Researcher basic information

• Doctor of Pharmaceutical Science, Kyoto University
• Master of Pharmaceutical Science, Kyoto University

• https://researchmap.jp/minami123?lang=en

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200901005509403864
• http://www.pharm.hokudai.ac.jp/yakuri/index.html

• 20243040

• 200901005509403864

• Depression
• Anxiety
• Thermobiology
• オピオイド
• モルヒネ
• 鎮痛
• 麻薬
• 情動
• 痛み
• 神経
• Opioid
• Morphine
• Analgesics
• Emotion
• Pain
• Narcotics
• Neuron

• Life Science, Pharmacology
• Life Science, Neuroscience-general

• Bachelor's degree program, School of Pharmaceutical Sciences and Pharmacy
• Master's degree program, Graduate School of Life Science
• Doctoral (PhD) degree program, Graduate School of Life Science

Research activity information

• 2003, 日本薬理学会学術奨励賞
  Japan
• 2001, 日本薬学会奨励賞
  Japan

• Addiction-related problems in Japan: A regional perspective.
  Soichiro Ide; Yoko Nishitani; Masahiko Sumitani; Masabumi Minami; Tadashi Isa; Masako Iseki; Michiko Ohkura; Hitoshi Okamoto; Tetsuro Kikuchi; Yuko Sekino; Hidehiko Takahashi; Kenji Takeuchi; Atsumi Nitta; Takeshi Honjo; Hiroshi Matsumoto; Tsuyoshi Miyakawa; Toshiya Murai; Toshihiko Matsumoto; Kazuyuki Nakagome; Kazutaka Ikeda
  Addiction (Abingdon, England), 30 Dec. 2025, [International Magazine]
  English, Scientific journal, Japan's addiction landscape appears paradoxical. The lifetime use of illicit drugs is among the lowest in Organisation for Economic Cooperation and Development countries, but harm from alcohol, tobacco, and gambling ranks among the world's highest. Historically, methamphetamine accounted for the majority of drug-related offenses, but the number of people who were apprehended for cannabis offenses in 2023 exceeded the number who were apprehended for stimulants for the first time since 1958. Nevertheless, the lifetime prevalence of illicit drug use among adults remains under ~3%. In contrast, heavy drinking among working-age men, decades of tobacco consumption, and rapid digitalization that has more recently led to a surge in online gambling and gaming disorder have imposed a substantial disease burden. The present review discusses Japan's epidemiology, social impact, policy changes, prevention, and treatment infrastructure of drug-related problems and the latest trends in addiction science and proposes ways to link policy and research. Japan's experience, balancing strict enforcement with health-centered care, may offer lessons for regions that have similar social contexts.
• In vivo imaging analyses to explore the integration of multimodal aversive sensory information in the central amygdala.
  Xinliang Zhou; Yuta Sakuragi; Chiaki Katagiri; Hiroshi Nomura; Masabumi Minami
  Scientific reports, 15, 1, 44348, 44348, 23 Dec. 2025, [International Magazine]
  English, Scientific journal, The negative emotions elicited by diverse aversive sensory stimuli induce avoidance behaviors and adaptive autonomic/hormonal responses, which are crucial for biological defense and homeostasis. The central amygdala (CeA), which receives a range of sensory information, plays important roles in stress and emotional responses. However, it remains unclear whether diverse sensory information from different sensory systems, such as the pain, olfactory, and gustatory systems, is received by the same group of CeA neurons and then integrated to generate negative emotions, or whether different neural pathways are used to generate negative emotions without converging on a specific group of CeA neurons. To clarify this issue, we conducted in vivo Ca2+ imaging to measure CeA neuron activity in response to aversive pain, olfactory, and gustatory stimuli. The results revealed that 144 of the 263 CeA neurons identified were activated by one or more types of aversive sensory stimuli: 70.8% of the activated neurons responded to only one stimulus, 24.3% to any two stimuli, and only 4.9% to all three, suggesting that the specificity of CeA neurons to aversive stimuli is relatively high, while some neurons respond multiple aversive stimuli. Aversive sensory information from different sensory pathways may be partially integrated in the CeA.
• Infraslow histaminergic dynamics govern priming states to gate moment-to-moment memory accessibility
  Yoshikazu Morishita; Yuki Takamura; Kyoka Nishimura; Yuto Yokoi; Yuya Ishihama; Rentaro Idutsu; Misato Ohno; Reika Matsumoto; Natsuko Hitora-Imamura; Masabumi Minami; Hiroshi Nomura
  Cold Spring Harbor Laboratory, 14 Nov. 2025
  Memory expression fluctuates even in response to identical cues, suggesting that ongoing brain states bias memory accessibility. However, the cellular and circuit principles governing these state-dependent fluctuations remain unclear. Here, we show that spontaneous pre-cue activity of histaminergic neurons in the hypothalamic tuberomammillary nucleus (TMN) modulates the expression of reward-associative memory in mice. TMN histaminergic activity exhibited infraslow dynamics (0.05-0.1 Hz) that closely tracked an integrated brain-body state. Closed-loop cue delivery during high histaminergic states enhanced memory expression. Brief optogenetic activation or inhibition of these neurons before the cue bidirectionally modulated memory expression, and direct activation of histaminergic terminals in the basolateral amygdala (BLA) was sufficient to enhance memory expression. Furthermore, histaminergic inhibition before the cue impaired the cue-evoked BLA population response. Thus, ongoing histaminergic activity exerts an infraslow, state-setting influence that primes BLA circuits for robust cue responses, and in turn, modulates moment-to-moment memory accessibility.
• Effects of MEK1/2 blocker U0126 on the medial preoptic synapse and behavioral selection of male mice.
  Yumi Hamasaki; Masabumi Minami; Taiju Amano
  Neuroscience research, 218, 104929, 104929, 28 Jun. 2025, [International Magazine]
  English, Scientific journal, The central part of the mouse medial preoptic area (cMPOA) is involved in parental behavior because the neurotoxic lesion of the cMPOA disturbed parental behavior and switched to infanticidal behavior. The cMPOA receives projection from many brain regions, including the medial amygdala (Me). We have previously found that optogenetic inhibition of the projection pathway from the Me to the cMPOA in virgin male mice suppressed the infanticidal behavior of virgin mice toward pups. Furthermore, electrophysiological analysis has revealed that intracellular signaling-mediated disinhibition occurs in the cMPOA neurons during the transition from virgin to father in gestation experience (FGE) mice. However, the specific downstream signal transduction pathway remains unclear. In this study, we utilized U0126, a MEK1/2 inhibitor, because U0126 has been reported to modulate GABAergic currents. Therefore, we examined the contribution of U0126 at the synaptic and behavioral levels. Applying U0126 to the cMPOA neurons in FGE mice restored eIPSP as much as that in cMPOA neurons in virgin mice. Furthermore, microinfusion of U0126 into the cMPOA shifted the behavioral pattern of FGE mice toward infanticide. These changes were not observed in the mice that experienced parenting. The results suggest that MEK1/2 mediates neurotransmission in the cMPOA and contributes to the stage transition from virgin to FGE mice after mating with females.
• Preventive and Therapeutic Effects of Intracerebroventricular Administration of Maresin-1 on Lipopolysaccharide-Induced Depression-Like Behaviors in Mice
  Satoshi Deyama; Katsuyuki Kaneda; Masabumi Minami
  Biological and Pharmaceutical Bulletin, 48, 1, 6, 10, Pharmaceutical Society of Japan, 11 Jan. 2025
  Scientific journal
• Preventive and Therapeutic Effects of Intracerebroventricular Administration of Maresin-1 on Lipopolysaccharide-Induced Depression-Like Behaviors in Mice.
  Satoshi Deyama; Katsuyuki Kaneda; Masabumi Minami
  Biological & pharmaceutical bulletin, 48, 1, 6, 10, 2025, [Domestic magazines]
  English, Scientific journal, Enhanced inflammatory and immune responses have been observed in patients with major depressive disorder, pointing to anti-inflammatory substances as potential seeds for developing novel antidepressants. Omega-3 polyunsaturated fatty acid metabolites, such as resolvin D and E series, maresins, and protectins (collectively known as specialized pro-resolving mediators) demonstrate anti-inflammatory effects. This study examined the antidepressant-like effects of maresin-1 (MaR1) on lipopolysaccharide (LPS)-induced depression-like behaviors in mice. Using the tail suspension test (TST) and the forced swim test (FST), we assessed depression-like behaviors 26 and 28 h after intraperitoneal injection of LPS (0.8 mg/kg), respectively. An open field test (OFT) was also conducted to evaluate locomotor activity 24 h after LPS injection. Intracerebroventricular (i.c.v.) injection of MaR1 (10 ng/mouse) immediately after the LPS challenge mitigated the increased immobility time in the TST and FST, without affecting locomotor activity in the OFT, indicating the preventive effects of MaR1 on LPS-induced depression-like behaviors. Furthermore, i.c.v. injection of MaR1 23 h after the LPS challenge reduced the immobility time in both tests, underscoring its therapeutic potential. These findings suggest that MaR1 could be a promising seed for developing novel antidepressants.
• レゾルビンE1によるうつ病治療の可能性
  Satoshi Deyama; Masabumi Minami; Katsuyuki Kaneda
  Folia Pharmacologica Japonica, 159, 4, 210, 213, Japanese Pharmacological Society, 01 Jul. 2024
  Scientific journal
• Chemogenetic activation of histamine neurons promotes retrieval of apparently lost memories.
  Yuto Yokoi; Ayame Kubo; Kyoka Nishimura; Yuki Takamura; Yoshikazu Morishita; Masabumi Minami; Hiroshi Nomura
  Molecular brain, 17, 1, 38, 38, 15 Jun. 2024, [International Magazine]
  English, Scientific journal, Memory retrieval can become difficult over time, but it is important to note that memories that appear to be forgotten might still be stored in the brain, as shown by their occasional spontaneous retrieval. Histamine in the central nervous system is a promising target for facilitating the recovery of memory retrieval. Our previous study demonstrated that histamine H3 receptor (H3R) inverse agonists/antagonists, activating histamine synthesis and release, enhance activity in the perirhinal cortex and help in retrieving forgotten long-term object recognition memories. However, it is unclear whether enhancing histaminergic activity alone is enough for the recovery of memory retrieval, considering that H3Rs are also located in other neuron types and affect the release of multiple neurotransmitters. In this study, we employed a chemogenetic method to determine whether specifically activating histamine neurons in the tuberomammillary nucleus facilitates memory retrieval. In the novel object recognition test, control mice did not show a preference for objects based on memory 1 week after training, but chemogenetic activation of histamine neurons before testing improved memory retrieval. This selective activation did not affect the locomotor activity or anxiety-related behavior. Administering an H2R antagonist directly into the perirhinal cortex inhibited the recovery of memory retrieval induced by the activation of histamine neurons. Furthermore, we utilized the Barnes maze test to investigate whether chemogenetic activation of histamine neurons influences the retrieval of forgotten spatial memories. Control mice explored all the holes in the maze equally 1 week after training, whereas mice with chemogenetically activated histamine neurons spent more time around the target hole. These findings indicate that chemogenetic activation of histamine neurons in the tuberomammillary nucleus can promote retrieval of seemingly forgotten object recognition and spatial memories.
• Chronic pain enhances excitability of corticotropin-releasing factor-expressing neurons in the oval part of the bed nucleus of the stria terminalis
  Ryoko Uchida; Yasutaka Mukai; Taiju Amano; Kenji Sakimura; Keiichi Itoi; Akihiro Yamanaka; Masabumi Minami
  Molecular Brain, 17, 1, Springer Science and Business Media LLC, 03 May 2024
  Scientific journal, Abstract
  
  We previously reported that enhanced corticotropin-releasing factor (CRF) signaling in the bed nucleus of the stria terminalis (BNST) caused the aversive responses during acute pain and suppressed the brain reward system during chronic pain. However, it remains to be examined whether chronic pain alters the excitability of CRF neurons in the BNST. In this study we investigated the chronic pain-induced changes in excitability of CRF-expressing neurons in the oval part of the BNST (ovBNST^CRF neurons) by whole-cell patch-clamp electrophysiology. CRF-Cre; Ai14 mice were used to visualize CRF neurons by tdTomato. Electrophysiological recordings from brain slices prepared from a mouse model of neuropathic pain revealed that rheobase and firing threshold were significantly decreased in the chronic pain group compared with the sham-operated control group. Firing rate of the chronic pain group was higher than that of the control group. These data indicate that chronic pain elevated neuronal excitability of ovBNST^CRF neurons.
• Experimental Approaches Used to Investigate Voluntary Behavioral Thermoregulatory Responses.
  Airi Ido; Minami Kanai; Natsuko Hitora-Imamura; Hiroshi Nomura; Masabumi Minami
  Advances in experimental medicine and biology, 1461, 189, 198, 2024, [International Magazine]
  English, Scientific journal, A new behavioral test was developed to investigate the neural mechanisms of voluntary, behavioral thermoregulatory responses. The apparatus used in this test consisted of a thermostatic chamber that maintained the ambient temperature at a chosen level and two side-by-side floor plates that were placed in the thermostatic chamber and could be set to different temperatures. As the three temperatures, ambient temperature and two plate temperatures, can be controlled independently, we term this behavioral test the three-temperature (3 T) test. When the ambient temperature was 28 °C with floor plate temperatures of 25 °C and 35 °C, mice showed preference to the warm plate over the cool one. By contrast, when the ambient temperature was 40 °C, the mice showed preference to the cool plate, that is, a cool-seeking behavior. Detailed analyses of the time courses of the plate preference and core body temperature revealed that this cool-seeking behavior contributed to the regulation of body temperature. By using the 3 T test in combination with the latest in vivo imaging techniques for real-time measurement of neuronal activities and neurotransmitter releases in the brain of freely-moving animals, the neural mechanisms of voluntary, behavioral thermoregulatory responses could be elucidated in the near future.
• [Resolvin E1 as a potential lead for the treatment of depression].
  Satoshi Deyama; Masabumi Minami; Katsuyuki Kaneda
  Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 159, 4, 210, 213, 2024, [Domestic magazines]
  Japanese, Scientific journal, Typical monoamine-based antidepressants have significant limitations, including a time lag for therapeutic response and low efficacy (more than one-third of depressed patients fail to respond to multiple antidepressant medications and are considered treatment-resistant). Conversely, ketamine, an N-methyl-D-aspartate receptor antagonist, exhibits rapid and sustained antidepressant actions in patients with treatment-resistant depression. However, clinical use of ketamine is limited due to its serious side effects. Thus, there is a significant need to develop novel ketamine-like antidepressants with fewer side effects. We previously demonstrated that intracerebroventricular infusion of resolvins (RvD1, RvD2, RvE1, RvE2, and RvE3), specialized pro-resolving lipid mediators derived from docosahexaenoic and eicosapentaenoic acids, produce antidepressant-like effects in mouse models of depression. Among resolvins, RvE1 produces the most potent antidepressant-like effects likely via ChemR23 in several mouse models of depression. Local infusion of RvE1 into the medial prefrontal cortex (mPFC) or dorsal hippocampal dentate gyrus (DG) also produces antidepressant-like effects, suggesting that these brain regions are sites of action of RvE1. Additionally, intranasal (i.n.) administration of RvE1 produces antidepressant-like effects through mechanisms similar to ketamine: activity-dependent release of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), and subsequent mechanistic target of rapamycin complex 1 (mTORC1) activation in the mPFC play a crucial role in the rapid and sustained antidepressant-like actions of i.n. RvE1. Moreover, the antidepressant-like effects of i.n. RvE1 require BDNF and VEGF release, but not mTORC1 activation, in the dorsal DG. These findings suggest that RvE1 can be a promising lead for a novel rapid-acting antidepressant.
• Evaluation of behavioural selection processes in conflict scenarios using a newly developed mouse behavioural paradigm.
  Yurika Miyagami; Yuki Honshuku; Hiroshi Nomura; Masabumi Minami; Natsuko Hitora-Imamura
  Scientific reports, 13, 1, 20006, 20006, 16 Nov. 2023, [International Magazine]
  English, Scientific journal, Selecting an appropriate behaviour is critical for survival in conflict scenarios, wherein animals face both appetitive and aversive stimuli. Behavioural selection consists of multiple processes: (1) animals remain quiet in a safe place to avoid aversive stimuli (suspension), (2) once they decide to take risks to approach appetitive stimuli, they assess the risks (risk assessment), and (3) they act to reach the reward. However, most studies have not addressed these distinct behavioural processes separately. Here, we developed a new experimental paradigm called the three-compartment conflict task to quantitatively evaluate conflict processes. Our apparatus consisted of start, flat, and grid compartments. Mice needed to explore the grid compartment, where they might receive foot shocks while trying to obtain sucrose. Applying foot shocks increased sucrose acquisition latency in subsequent trials, reflecting elevated conflict levels throughout trials. The time spent in the start compartment and the number of retreats were determined to measure the conflict levels in suspension and risk assessment, respectively. Foot shocks increased these parameters, whereas diazepam decreased them. Our new paradigm is valuable for quantitatively evaluating distinct behavioural processes and contributes to developing effective treatments for psychiatric disorders associated with maladaptive behaviours in conflict scenarios.
• Synaptic plasticity in the medial preoptic area of male mice encodes social experiences with female and regulates behavior toward young
  Kazuki Ito; Keiichiro Sato; Yousuke Tsuneoka; Takashi Maejima; Hiroyuki Okuno; Yumi Hamasaki; Shunsaku Murakawa; Yuzu Takabayashi; Chihiro Yoshihara; Sayaka Shindo; Haruka Uki; Stefan Herlitze; Masahide Seki; Yutaka Suzuki; Takeshi Sakurai; Kumi O Kuroda; Masabumi Minami; Taiju Amano
  Cold Spring Harbor Laboratory, 24 Oct. 2023
  Summary
  
  A dramatic shift from aggressive infanticidal to paternal behaviors is an essential event for male mice after mating. While the central part of the medial preoptic area (cMPOA) has been shown to critically mediate the paternal behaviors in mice, how this brain region becomes activated by mating and subsequent interaction with pups has not been investigated. Here, we demonstrate that the reduction in inhibitory synaptic strength towards the cMPOA provided by posterior-dorsal medial amygdala (MePD) neurons is a key event for the post-mating behavioral shift in males. Consistent with this, we found optogenetic disinhibition of Me^Cartptto the cMPOA synapses reduces male aggression towards pups. The cMPOA of paternal mice mediated pup-induced neural plastic changes in the bed nucleus of the stria terminalis. These findings provide possible functions of cMPOA neural circuits required for the reception to young in male mice.
• 炎症による抑うつ様症状の自発的治癒におけるGPR18の役割
  出山 諭司; 南 雅文; 金田 勝幸
  日本神経精神薬理学会年会プログラム・抄録集, 53回, 169, 169, (一社)日本神経精神薬理学会, Sep. 2023
  Japanese
• Intranasal administration of resolvin E1 produces antidepressant-like effects via BDNF/VEGF-mTORC1 signaling in the medial prefrontal cortex.
  Deyama S; Aoki S; Sugie R; Fukuda H; Shuto S; Minami M; Kaneda K
  Neurotherapeutics, in press, 2023, [Peer-reviewed]
• Distinct neuronal populations mediate parenting and infanticide in the amygdalohippocampal area
  Keiichiro Sato; Hiroyuki Okuno; Kazune Kitamura; Haruhiko Bito; Yutaka Suzuki; Masabumi Minami; Taiju Amano
  Research Square Platform LLC, 15 Dec. 2022
  Abstract
  
  Male animals exhibit positive and negative infant-directed behaviors, yet the underlying neural mechanisms remain unknown. The amygdalohippocampal area (AHi) regulates social behavior through neural projections to multiple brain regions. Although AHi neurons that project to the medial preoptic area (MPOA) were reported to promote infanticide in male mice, MPOA-projecting AHi neurons are activated by both parenting and infanticide, suggesting heterogeneity within these neurons. Here using a newly developed, virus-mediated projection-specific and activity-dependent cell labeling method (vPAL), we uncovered two distinct functional, electrophysiological, and transcriptional populations in MPOA-projecting AHi neurons, designated infanticide-related and parenting-related neurons. Furthermore, activation of serotonin receptor 7, which is highly expressed in parenting neurons, selectively suppressed infanticide while promoting parenting in virgin male mice. This study provides a better understanding of the neuronal populations, functions, and properties that previous labeling methods masked.
• Resolution of depression: antidepressant actions of resolvins.
  Satoshi Deyama; Katsuyuki Kaneda; Masabumi Minami
  Neuroscience research, 19 Oct. 2022, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Major depressive disorder, one of the most widespread mental illnesses, brings about enormous individual and socioeconomic consequences. Conventional monoaminergic antidepressants require weeks to months to produce a therapeutic response, and approximately one-third of the patients fail to respond to these drugs and are considered treatment-resistant. Although recent studies have demonstrated that ketamine, an N-methyl-D-aspartate receptor antagonist, produces rapid antidepressant effects in treatment-resistant patients, it also has undesirable side effects. Hence, rapid-acting antidepressants that have fewer adverse effects than ketamine are urgently required. D-series (RvD1-RvD6) and E-series (RvE1-RvE4) resolvins are endogenous lipid mediators derived from docosahexaenoic and eicosapentaenoic acids, respectively. These mediators reportedly play a pivotal role in the resolution of acute inflammation. In this review, we reveal that intracranial infusions of RvD1, RvD2, RvE1, RvE2, and RvE3 produce antidepressant-like effects in various rodent models of depression. Moreover, the behavioral effects of RvD1, RvD2, and RvE1 are mediated by the activation of the mechanistic target of rapamycin complex 1, which is essential for the antidepressant-like actions of ketamine. Finally, we briefly provide our perspective on the possible role of endogenous resolvins in stress resilience.
• 【アディクションへの包括的な取り組み】わが国におけるアディクション研究の方向性
  井手 聡一郎; 伊佐 正; 西谷 陽子; 南 雅文; 村井 俊哉; 高橋 英彦; 宮田 久嗣; 久我 弘典; 松本 俊彦; 中込 和幸; 池田 和隆
  精神科, 41, 2, 279, 285, (有)科学評論社, Aug. 2022
  Japanese
• The impact of pitolisant, an H3 receptor antagonist/inverse agonist, on perirhinal cortex activity in individual neuron and neuronal population levels.
  Kyosuke Hirano; Yoshikazu Morishita; Masabumi Minami; Hiroshi Nomura
  Scientific reports, 12, 1, 7015, 7015, 12 May 2022, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Histamine is a neurotransmitter that modulates neuronal activity and regulates various brain functions. Histamine H3 receptor (H3R) antagonists/inverse agonists enhance its release in most brain regions, including the cerebral cortex, which improves learning and memory and exerts an antiepileptic effect. However, the mechanism underlying the effect of H3R antagonists/inverse agonists on cortical neuronal activity in vivo remains unclear. Here, we show the mechanism by which pitolisant, an H3R antagonist/inverse agonist, influenced perirhinal cortex (PRh) activity in individual neuron and neuronal population levels. We monitored neuronal activity in the PRh of freely moving mice using in vivo Ca2+ imaging through a miniaturized one-photon microscope. Pitolisant increased the activity of some PRh neurons while decreasing the activity of others without affecting the mean neuronal activity across neurons. Moreover, it increases neuron pairs with synchronous activity in excitatory-responsive neuronal populations. Furthermore, machine learning analysis revealed that pitolisant altered the neuronal population activity. The changes in the population activity were dependent on the neurons that were excited and inhibited by pitolisant treatment. These findings indicate that pitolisant influences the activity of a subset of PRh neurons by increasing the synchronous activity and modifying the population activity.
• Chronic pain-induced neuronal plasticity in the bed nucleus of the stria terminalis causes maladaptive anxiety.
  Naoki Yamauchi; Keiichiro Sato; Kenta Sato; Shunsaku Murakawa; Yumi Hamasaki; Hiroshi Nomura; Taiju Amano; Masabumi Minami
  Science advances, 8, 17, eabj5586, 29 Apr. 2022, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, Scientific journal, The comorbidity of chronic pain and mental dysfunctions such as depression and anxiety disorders has long been recognized, but the underlying mechanisms remain poorly understood. Here, using a mouse model of neuropathic pain, we demonstrated neuronal plasticity in the bed nucleus of the stria terminalis (BNST), which plays a critical role in chronic pain-induced maladaptive anxiety. Electrophysiology demonstrated that chronic pain increased inhibitory inputs to lateral hypothalamus (LH)-projecting BNST neurons. Chemogenetic manipulation revealed that sustained suppression of LH-projecting BNST neurons played a crucial role in chronic pain-induced anxiety. Furthermore, using a molecular genetic approach, we demonstrated that chronic pain elevated the excitability of a specific subpopulation of BNST neurons, which express cocaine- and amphetamine-regulated transcript (CART). The elevated excitability of CART-positive neurons caused the increased inhibitory inputs to LH-projecting BNST neurons, thereby inducing anxiety-like behavior. These findings shed light on how chronic pain induces psychiatric disorders, characterized by maladaptive anxiety.
• The antidepressant-like effect of resolvin E1 in repeated prednisolone-induced depression model mice.
  Shun Aoki; Satoshi Deyama; Rinako Sugie; Kohei Ishimura; Hayato Fukuda; Satoshi Shuto; Masabumi Minami; Katsuyuki Kaneda
  Behavioural brain research, 418, 113676, 113676, 10 Feb. 2022, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Resolvin E1 (RvE1) is an anti-inflammatory lipid mediator derived from eicosapentaenoic acid. We previously demonstrated that intracerebroventricular (i.c.v.) and intra-medial prefrontal cortex (mPFC) infusions of RvE1 produce antidepressant-like effects in a lipopolysaccharide-induced depression mouse model. To further confirm the antidepressant-like effect of RvE1, the present study examined whether RvE1 ameliorated depression-like behavior induced by repeated injections of prednisolone (PSL), a synthetic glucocorticoid, in male ICR mice. We first ascertained whether repeated subcutaneous treatment with PSL (50 mg/kg, once a day) affected locomotor activity and anxiety-like behavior in the open field test (OFT; after a 5-day PSL treatment) and induced depression-like behavior in the tail suspension test (TST; after a 6-day PSL treatment) and forced swim test (FST; after a 7-day PSL treatment). Repeated PSL injections significantly increased immobility in the FST, which was not ameliorated by acute desipramine treatment (30 mg/kg, i.p.), but not in the TST, without affecting locomotor activity and anxiety-like behavior in the OFT. Subsequently, we investigated the therapeutic effects of i.c.v. (1 ng) and intra-mPFC (50 pg/side) infusions of RvE1 in the repeated PSL-induced depression mouse model using the OFT and FST after 5- and 6-day PSL treatments, respectively. The repeated PSL-induced increase in immobility in the FST was significantly attenuated by both i.c.v. and intra-mPFC infusions of RvE1 without affecting the locomotor activity and anxiety-like behavior. In addition, a single i.c.v. infusion of RvE1 immediately before the first or fourth injection of PSL also attenuated PSL-induced depression-like behavior in the FST, suggesting the preventive effect of RvE1. These results indicate that RvE1 produces antidepressant-like effects in a mouse model of repeated PSL-induced depression.
• Exposure to hot and cold environments activates neurons projecting from the paraventricular thalamic nucleus to brain regions related to approach and avoidance behaviors.
  Minami Kanai; Ryota Kamiizawa; Natsuko Hitora-Imamura; Masabumi Minami
  Journal of thermal biology, 103, 103157, 103157, Jan. 2022, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, Scientific journal, Although cool- and warm-seeking behaviors for behavioral thermoregulation are considered to be appetitive/approach and aversive/avoidance behaviors, the neuronal circuits mediating such behaviors remain to be elucidated. A growing body of evidence suggests that the paraventricular thalamic nucleus (PVT) is a key brain region in a neuronal circuit that mediates appetitive/approach and aversive/avoidance behaviors. In this study, to elucidate the neuronal circuits mediating behavioral thermoregulatory responses, we examined whether neuronal pathways from the PVT to the nucleus accumbens (NAc), bed nucleus of the stria terminalis (BNST), and central nucleus of the amygdala (CeA), which are brain regions implicated in mediating appetitive/approach and aversive/avoidance behaviors, are activated during exposure to hot (38°C) and cold (8°C) environments using c-Fos immunostaining and retrograde tracing. Our results showed activation of neuronal pathways from the PVT to the NAc, BNST, and CeA during exposure to hot and cold environments, suggesting that activation of these pathways may be involved in avoidance behaviors from hot and cold environments for behavioral thermoregulation.
• Estrogen signaling modulates behavioral selection toward pups and amygdalohippocampal area in the rhomboid nucleus of the bed nucleus of the stria terminalis circuit.
  Kiyoshiro Fukui; Keiichiro Sato; Shunsaku Murakawa; Masabumi Minami; Taiju Amano
  Neuropharmacology, 108879, 108879, 13 Nov. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Gonadal steroid hormone influences behavioral choice of adult animals toward pups, parental or aggressive. We previously reported that long-term administration of 17β-estradiol (E2) to male mice during sexual maturation induces aggressive behavior toward conspecific pups, which is called "infanticide," and significantly enhanced excitatory synaptic transmission in the rhomboid nucleus of bed nucleus of stria terminalis (BSTrh), which is an important brain region for infanticide. However, it is unclear how estrogen receptor-dependent signaling after sexual maturity regulates neural circuits including the BSTrh. Here we revealed that E2 administration to gonadectomized mice in adulthood elicited infanticidal behavior and enhanced excitatory synaptic transmission in the BSTrh by increasing the probability of glutamate release from the presynaptic terminalis. Next, we performed whole-brain mapping of E2-sensitive brain regions projecting to the BSTrh and found that amygdalohippocampal area (AHi) neurons that project to the BSTrh densely express estrogen receptor 1 (Esr1). Moreover, E2 treatment enhanced synaptic connectivity in the AHi-BSTrh pathway. Together, these results suggest that reinforcement of excitatory inputs from AHi neurons into the BSTrh by estrogen receptor-dependent signaling may contribute to the expression of infanticide.
• Resolvin E1 Attenuates Chronic Pain-Induced Depression-Like Behavior in Mice: Possible Involvement of Chemerin Receptor ChemR23
  Hiroe Suzuki; Takahisa Otsuka; Natsuko Hitora-Imamura; Kohei Ishimura; Hayato Fukuda; Koichi Fujiwara; Satoshi Shuto; Satoshi Deyama; Masabumi Minami
  Biological and Pharmaceutical Bulletin, 44, 10, 1548, 1550, Pharmaceutical Society of Japan, 01 Oct. 2021, [Peer-reviewed], [Last author, Corresponding author], [Domestic magazines]
  English, Scientific journal, The antidepressant effect of eicosapentaenoic acid-derived bioactive lipid, resolvin E1 (RvE1), was examined in a murine model of chronic pain-induced depression using a tail suspension test. Because RvE1 reportedly possesses agonistic activity on a chemerin receptor ChemR23, we also examined the antidepressant effect of chemerin. Two weeks after surgery for unilateral spared nerve injury to prepare neuropathic pain model mice, immobility time was measured in a tail suspension test. Chronic pain significantly increased immobility time, and this depression-like behavior was attenuated by intracerebroventricular injection of RvE1 (1 ng) or chemerin (500 ng). These results demonstrate that RvE1 exerts an antidepressant effect in a murine model of chronic pain-induced depression, which is likely to be via ChemR23. RvE1 and its receptor may be promising targets to develop novel antidepressants.
• Resolvins as potential candidates for the treatment of major depressive disorder
  Satoshi Deyama; Masabumi Minami; Katsuyuki Kaneda
  Journal of Pharmacological Sciences, 147, 1, 33, 39, Elsevier BV, Sep. 2021, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, In contrast with the delayed onset of therapeutic responses and relatively low efficacy of currently available monoamine-based antidepressants, a single subanesthetic dose of ketamine, an N-methyl-D-aspartate receptor antagonist, produces rapid and sustained antidepressant actions even in patients with treatment-resistant depression. However, since the clinical use of ketamine as an antidepressant is limited owing to its adverse effects, such as psychotomimetic/dissociative effects and abuse potential, there is an unmet need for novel rapid-acting antidepressants with fewer side effects. Preclinical studies have revealed that the antidepressant actions of ketamine are mediated via the release of brain-derived neurotrophic factor and vascular endothelial growth factor, with the subsequent activation of mechanistic target of rapamycin complex 1 (mTORC1) in the medial prefrontal cortex. Recently, we demonstrated that resolvins (RvD1, RvD2, RvE1, RvE2 and RvE3), endogenous lipid mediators generated from n-3 polyunsaturated fatty acids (docosahexaenoic and eicosapentaenoic acids), exert antidepressant effects in a rodent model of depression, and that the antidepressant effects of RvD1, RvD2, and RvE1 necessitate mTORC1 activation. In this review, we first provide an overview of the mechanisms underlying the antidepressant effects of ketamine and other rapid-acting agents. We then discuss the possibility of using resolvins as novel therapeutic candidates for depression.
• Resolvin D2 attenuates chronic pain–induced depression‐like behavior in mice
  Hiroe Suzuki; Natsuko Hitora‐Imamura; Satoshi Deyama; Masabumi Minami
  Neuropsychopharmacology Reports, 41, 3, 426, 429, Wiley, Sep. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, Scientific journal, AIM: We previously demonstrated that intracerebroventricular injection of resolvin D2 (RvD2), a bioactive lipid mediator derived from docosahexaenoic acid, ameliorated depression-like behavior in lipopolysaccharide-induced and chronic mild stress-induced mouse models of depression. In the present study, we examined the antidepressant effect of RvD2 on chronic pain-induced depression-like behavior. METHODS: To prepare the neuropathic pain model, mice were subjected to surgery for unilateral spared nerve injury. Two weeks after surgery, the antidepressant effect of RvD2 was examined using the tail suspension test. RESULTS: Chronic pain significantly increased immobility time, and this depression-like behavior was attenuated by intracerebroventricular injection of RvD2 (10 ng). No effect of RvD2 on the locomotor activity was observed. CONCLUSION: RvD2 produces an antidepressant effect in a murine model of chronic pain-induced depression and may be a promising lead for the development of novel antidepressants.
• Diverse intracellular signaling pathways mediate the effects of neurotensin on the excitability of type II neurons in the rat dorsolateral bed nucleus of the stria terminalis
  Tomoyuki Kaneko; Ryuto Hara; Taiju Amano; Masabumi Minami
  Journal of Pharmacological Sciences, 147, 1, 86, 94, Elsevier BV, Sep. 2021, [Peer-reviewed], [Last author, Corresponding author]
  Scientific journal
• Inhibitory synaptic transmissions to the bed nucleus of the stria terminalis neurons projecting to the ventral tegmental area are enhanced in rats exposed to chronic mild stress
  Ryuto Hara; Daiki Takahashi; Tatsuhiro Takehara; Taiju Amano; Masabumi Minami
  Molecular Brain, 13, 1, Springer Science and Business Media LLC, Dec. 2020, [Peer-reviewed], [Last author, Corresponding author]
  Scientific journal,
  The comorbidities of depression and chronic pain have long been recognized in the clinic, and several preclinical studies have demonstrated depression-like behaviors in animal models of chronic pain. These findings suggest a common neuronal basis for depression and chronic pain. Recently, we reported that the mesolimbic dopaminergic system was tonically suppressed during chronic pain by enhanced inhibitory synaptic inputs to neurons projecting from the dorsolateral bed nucleus of the stria terminalis (dlBNST) to the ventral tegmental area (VTA), suggesting that tonic suppression of the mesolimbic dopaminergic system by this neuroplastic change may be involved in chronic pain-induced depression-like behaviors. In this study, we hypothesized that inhibitory synaptic inputs to VTA-projecting dlBNST neurons are also enhanced in animal models of depression, thereby suppressing the mesolimbic dopaminergic system. To test this hypothesis, we performed whole-cell patch-clamp electrophysiology using brain slices prepared from rats exposed to chronic mild stress (CMS), a widely used animal model of depression. The results showed a significant enhancement in the frequency of spontaneous inhibitory postsynaptic currents in VTA-projecting dlBNST neurons in the CMS group compared with the no stress group. The findings revealed enhanced inhibitory synaptic inputs to VTA-projecting dlBNST neurons in this rat model of depression, suggesting that this neuroplastic change is a neuronal mechanism common to depression and chronic pain that causes dysfunction of the mesolimbic dopaminergic system, thereby inducing depression-like behaviors.
• Noradrenaline enhances the excitatory effects of dopamine on medial prefrontal cortex pyramidal neurons in rats
  Fumiya Shinohara; Saya Arakaki; Taiju Amano; Masabumi Minami; Katsuyuki Kaneda
  Neuropsychopharmacology Reports, 40, 4, 348, 354, Wiley, Dec. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, AIM: Our previous studies showed that exposure to acute restraint stress enhanced cocaine-induced conditioned place preference (cocaine-CPP) and suggested the possibility that co-activation of adrenergic transmission boosts the increase in medial prefrontal cortex (mPFC) neuronal activity by the activation of dopaminergic transmission. To examine this possibility, the effects of the co-treatment with dopamine (DA) and noradrenaline (NA) on mPFC neurons were compared with those of treatment with DA alone using whole-cell patch-clamp recordings. METHODS: The effects of DA alone and a mixture of DA and NA on the membrane potentials and spontaneous excitatory postsynaptic currents (sEPSCs) were examined by electrophysiological recordings of mPFC pyramidal neurons in brain slices of male Sprague Dawley rats. Extracellular DA and NA levels in the mPFC during and after restraint stress exposure were also examined by in vivo microdialysis. RESULTS: Dopamine significantly produced depolarizing effects on mPFC neurons and tended to increase sEPSC frequency. Co-administration of NA with DA produced stronger depolarizing effects and significantly increased sEPSC frequency. The findings suggest that the additional depolarizing effect of NA on DA-responsive neurons, rather than the excitation of DA-nonresponsive neurons by NA, contributes to the stronger effect of co-treatment of NA with DA. CONCLUSION: The present study suggests that NA released by restraint stress exposure cooperates with DA to stimulate DA-responsive neurons in the mPFC, thereby causing the stress-induced enhancement of cocaine-CPP.
• Disappearance of the inhibitory effect of neuropeptide Y within the dorsolateral bed nucleus of the stria terminalis in rats with chronic pain.
  Ryuto Hara; Yuta Asaoka; Daiki Takahashi; Hiroshi Nomura; Taiju Amano; Masabumi Minami
  Neuroscience letters, 728, 134958, 134958, 09 Apr. 2020, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, We recently showed that the mesolimbic dopaminergic system was tonically suppressed during chronic pain by enhanced corticotropin releasing factor (CRF) signaling within the dorsolateral bed nucleus of the stria terminalis (dlBNST), and that inhibition of intra-dlBNST CRF signaling restored the mesolimbic dopaminergic system function. Specifically, bilateral intra-dlBNST injections of the CRF type 1 receptor antagonist NBI27914 increased intra-nucleus accumbens dopamine release and induced reward-related behaviors in rats with chronic pain. Here, we used a conditioned place preference (CPP) test to explore whether intra-dlBNST injections of neuropeptide Y (NPY) restored the mesolimbic reward system function in chronic pain rats, because we previously showed that NPY had an effect opposite to that of CRF in dlBNST neurons. Specifically, CRF depolarized type II dlBNST neurons whereas NPY hyperpolarized them. However, unexpectedly, intra-dlBNST NPY injections had no effect on CPP test outcomes. Then, we compared the effects of NPY on the membrane potentials of type II dlBNST neurons of sham-operated control rats and those of chronic pain animals. Whole-cell patch-clamp electrophysiology revealed that NPY hyperpolarized type II dlBNST neurons in the sham-operated group. By contrast, in the chronic pain group, NPY did not hyperpolarize, but rather depolarized, type II dlBNST neurons. These results indicate that NPY no longer hyperpolarizes type II dlBNST neurons in rats with chronic pain, therefore it does not reverse the excitatory effects of CRF. This may be why intra-dlBNST injections of NPY into chronic pain rats did not exhibit a rewarding effect in the CPP test, whereas intra-dlBNST injections of NBI27914 did. This is the first study to demonstrate a chronic pain-induced neuroplastic change in NPY signaling in the dlBNST. Such a change may be involved in the dysfunction of the mesolimbic reward system under the chronic pain condition.
• Amygdalohippocampal area neurons that project to the preoptic area mediate infant-directed attack in male mice.
  Keiichiro Sato; Yumi Hamasaki; Kiyoshiro Fukui; Kazuki Ito; Kazunari Miyamichi; Masabumi Minami; Taiju Amano
  The Journal of neuroscience : the official journal of the Society for Neuroscience, 40, 20, 3981, 3994, 07 Apr. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Male animals may show alternative behaviors toward infants, attack or parenting. These behaviors are triggered by pup stimuli under the influence of the internal state, including the hormonal environment and/or social experiences. Converging data suggest that the medial preoptic area (MPOA) contributes to the behavioral selection toward the pup. However, the neural mechanisms underlying how integrated stimuli affect the MPOA-dependent behavioral selection remain unclear.Here we focus on the amygdalohippocampal area (AHi) that projects to MPOA and expresses oxytocin receptor, a hormone receptor mediating social behavior toward pups. We describe the activation of MPOA-projection AHi neurons in male mice by social contact with pups. Input mapping using the TRIO method reveals that MPOA-projection AHi neurons receive prominent inputs from several regions, including the thalamus, hypothalamus, and olfactory cortex. Electrophysiological and histological analysis demonstrates that oxytocin modulates inhibitory synaptic responses on MPOA-projection AHi neurons. In addition, AHi forms the excitatory mono-synapse to MPOA, and pharmacological activation of MPOA-projection AHi neurons enhances only aggressive behavior, but not parental behavior. Interestingly, this promoted behavior was related to social experience in male mice. Collectively, our results identified a pre-synaptic partner of MPOA that can integrate sensory input and hormonal state, and trigger pup-directed aggression.Significance statementThe medial preoptic area (MPOA) plays critical roles in parental behavior, such as motor control, motivation, and social interaction. The MPOA projects to multiple brain regions, and these projections contribute to several neural controls in parental behavior. In contrast, how inputs to MPOA are regulated by social and environmental information is poorly understood. In this study, we focus on the area of amygdalohippocampal area (AHi) that connects to MPOA and expresses oxytocin receptor. We demonstrate the disruption of the expression of parental behavior triggered by the activation of MPOA-projection AHi neurons. This behavior may be regulated by not only oxytocin but also neural input from several regions.
• Acute restraint stress augments the rewarding memory of cocaine through activation of α1 adrenoceptors in the medial prefrontal cortex of mice.
  Shintaro Wada; Junko Yanagida; Hitoki Sasase; Tong Zhang; Xueting Li; Hironori Kamii; Masaki Domoto; Satoshi Deyama; Eiichi Hinoi; Akihiro Yamanaka; Naoya Nishitani; Kazuki Nagayasu; Shuji Kaneko; Masabumi Minami; Katsuyuki Kaneda
  Neuropharmacology, 166, 107968, 107968, Apr. 2020, [Peer-reviewed], [International Magazine]
  English, Stress augments the rewarding memory of cocaine, which plays a critical role in inducing cocaine craving. However, the neurobiological mechanisms underlying the enhancing effect of stress remain unclear. Here, we show that noradrenaline (NA) transmission in the medial prefrontal cortex (mPFC) mediates stress-induced enhancement of cocaine craving. When mice were exposed to acute restraint stress immediately before the posttest session of the cocaine-induced conditioned place preference (CPP) paradigm, the CPP score was significantly higher than that in non-stressed mice. Because extracellular NA levels have been reported to be increased in the mPFC during stress exposure, we assessed the effects of NA on mPFC layer 5 pyramidal cell activity. Whole-cell recordings revealed that NA application induces depolarization and a concomitant increase in spontaneous excitatory postsynaptic currents (sEPSCs). The NA effects were inhibited by terazosin, but not by yohimbine or timolol, and the sEPSC increase was not observed in the presence of tetrodotoxin, suggesting the involvement of postsynaptic α1, but not α2 or β, adrenoceptors in the NA effects. Additionally, intra-mPFC injection of terazosin before stress exposure attenuated the stress-induced increase in cocaine CPP. Intra-mPFC injection of phenylephrine, an α1 adrenoceptor agonist, before the posttest session without stress exposure significantly enhanced cocaine CPP. Furthermore, chemogenetic suppression of mPFC pyramidal cells with inhibitory DREADD (designer receptors exclusively activated by designer drugs) also suppressed the stress-induced CPP enhancement. These findings suggest that the stress-induced increase in NA transmission activates mPFC pyramidal cells via α1 adrenoceptor stimulation, leading to enhancement of cocaine craving-related behavior.
• Glutamatergic neurons in the medial prefrontal cortex mediate the formation and retrieval of cocaine-associated memories in mice.
  Zhang T; Yanagida J; Kamii H; Wada S; Domoto M; Sasase H; Deyama S; Takarada T; Hinoi E; Sakimura K; Yamanaka A; Maejima T; Mieda M; Sakurai T; Nishitani N; Nagayasu K; Kaneko S; Minami M; Kaneda K
  Addiction Biology, 25, 1, e12723, Jan. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, In drug addiction, environmental stimuli previously associated with cocaine use readily elicit cocaine-associated memories, which persist long after abstinence and trigger cocaine craving and consumption. Although previous studies suggest that the medial prefrontal cortex (mPFC) is involved in the expression of cocaine-addictive behaviors, it remains unclear whether excitatory and inhibitory neurons in the mPFC are causally related to the formation and retrieval of cocaine-associated memories. To address this issue, we used the designer receptors exclusively activated by designer drugs (DREADD) technology combined with a cocaine-induced conditioned place preference (CPP) paradigm. We suppressed mPFC neuronal activity in a cell-type- and timing-dependent manner. C57BL/6J wild-type mice received bilateral intra-mPFC infusion of an adeno-associated virus (AAV) expressing inhibitory DREADD (hM4Di) under the control of CaMKII promotor to selectively suppress mPFC pyramidal neurons. GAD67-Cre mice received bilateral intra-mPFC infusion of a Cre-dependent AAV expressing hM4Di to specifically silence GABAergic neurons. Chemogenetic suppression of mPFC pyramidal neurons significantly attenuated both the acquisition and expression of cocaine CPP, while suppression of mPFC GABAergic neurons affected neither the acquisition nor expression of cocaine CPP. Moreover, chemogenetic inhibition of mPFC glutamatergic neurons did not affect the acquisition and expression of lithium chloride-induced conditioned place aversion. These results suggest that the activation of glutamatergic, but not GABAergic, neurons in the mPFC mediates both the formation and retrieval of cocaine-associated memories.
• Tonic suppression of the mesolimbic dopaminergic system by enhanced corticotropin-releasing factor signaling within the bed nucleus of the stria terminalis in chronic pain model rats.
  Daiki Takahashi; Yuta Asaoka; Keisuke Kimura; Ryuto Hara; Saya Arakaki; Keisuke Sakasai; Hiroe Suzuki; Naoki Yamauchi; Hiroshi Nomura; Taiju Amano; Masabumi Minami
  The Journal of Neuroscience, 39, 42, 8376, 8385, Oct. 2019, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Effect of gonadal steroid hormone levels during pubertal development on social behavior of adult mice toward pups and synaptic transmission in the rhomboid nucleus of the bed nucleus of the stria terminalis.
  Kiyoshiro Fukui; Haruka Uki; Masabumi Minami; Taiju Amano
  Neuroscience Letters, 708, 134357, Aug. 2019, [Peer-reviewed]
  English, Scientific journal
• Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories.
  Hiroshi Nomura; Hiroto Mizuta; Hiroaki Norimoto; Fumitaka Masuda; Yuki Miura; Ayame Kubo; Hiroto Kojima; Aoi Ashizuka; Noriko Matsukawa; Zohal Baraki; Natsuko Hitora-Imamura; Daisuke Nakayama; Tomoe Ishikawa; Mami Okada; Ken Orita; Ryoki Saito; Naoki Yamauchi; Yamato Sano; Hiroyuki Kusuhara; Masabumi Minami; Hidehiko Takahashi; Yuji Ikegaya
  Biological psychiatry, 86, 3, 230, 239, 01 Aug. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND: A method that promotes the retrieval of lost long-term memories has not been well established. Histamine in the central nervous system is implicated in learning and memory, and treatment with antihistamines impairs learning and memory. Because histamine H3 receptor inverse agonists upregulate histamine release, the inverse agonists may enhance learning and memory. However, whether the inverse agonists promote the retrieval of forgotten long-term memory has not yet been determined. METHODS: Here, we employed multidisciplinary methods, including mouse behavior, calcium imaging, and chemogenetic manipulation, to examine whether and how the histamine H3 receptor inverse agonists, thioperamide and betahistine, promote the retrieval of a forgotten long-term object memory in mice. In addition, we conducted a randomized double-blind, placebo-controlled crossover trial in healthy adult participants to investigate whether betahistine treatment promotes memory retrieval in humans. RESULTS: The treatment of H3 receptor inverse agonists induced the recall of forgotten memories even 1 week and 1 month after training in mice. The memory recovery was mediated by the disinhibition of histamine release in the perirhinal cortex, which activated the histamine H2 receptor. Histamine depolarized perirhinal cortex neurons, enhanced their spontaneous activity, and facilitated the reactivation of behaviorally activated neuronal ensembles. A human clinical trial revealed that treatment of H3 receptor inverse agonists is specifically more effective for items that are more difficult to remember and subjects with poorer performance. CONCLUSIONS: These results highlight a novel interaction between the central histamine signaling and memory engrams.
• The role of the bed nucleus of the stria terminalis in pain-induced aversive motivation
  Masabumi Minami
  Current Opinion in Behavioral Sciences, 26, 46, 53, Elsevier BV, Apr. 2019, [Peer-reviewed], [Lead author, Last author, Corresponding author]
  Scientific journal
• Prior observation of fear learning enhances subsequent self-experienced fear learning with an overlapping neuronal ensemble in the dorsal hippocampus.
  Nomura H; Teshirogi C; Nakayama D; Minami M; Ikegaya Y
  Molecular brain, 12, 1, 21, Mar. 2019, [Peer-reviewed]
• Exposure to hot and cold environments increases noradrenaline release in the bed nucleus of the stria terminalis in rats.
  Minami S; Nomura H; Minami M
  Neuropsychopharmacology reports, Oct. 2018, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Roles of noradrenergic transmission within the ventral part of the bed nucleus of the stria terminalis in bidirectional brain-intestine interactions.
  Ide S; Yamamoto R; Suzuki H; Takeda H; Minami M
  Neuropsychopharmacology reports, 38, 4, 182, 188, Sep. 2018, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, Scientific journal, AIMS: The bed nucleus of the stria terminalis (BNST) is a limbic structure mediating autonomic and neuroendocrine responses and negative affective states such as anxiety and fear. We previously demonstrated that noradrenergic transmission via β-adrenoceptors within the ventral part of BNST (vBNST) is involved in bidirectional interactions between the brain and the upper gastrointestinal (GI) tract. The present study aimed to examine the roles of intra-vBNST noradrenergic transmission via β-adrenoceptors in bidirectional interactions between the brain and lower GI tract. METHODS: In vivo microdialysis experiments were performed to examine colorectal distention (CRD)-induced noradrenaline release within the vBNST of freely moving male Sprague-Dawley rats. Colonic transit and abdominal pain perception were examined following intra-vBNST injections of isoproterenol, a β-adrenoceptor agonist, with and without co-administration of timolol, a β-adrenoceptor antagonist. RESULTS: CRD increased extracellular noradrenaline levels within the vBNST and evoked abdominal contractions in a pressure-dependent manner (30-60 mm Hg). Bilateral intra-vBNST injections of isoproterenol (30 nmol/side) significantly increased CRD (30 mm Hg)-induced abdominal contractions. Intra-vBNST injections of isoproterenol (30 nmol/side) significantly increased colonic transit, which was reversed by co-administration of timolol (30 nmol/side). CONCLUSION: The results of this study suggest (a) the existence of a positive feedback loop between intra-vBNST noradrenaline release and abdominal pain perception, and (b) the modulation of colonic motility by intra-vBNST noradrenergic transmission via β-adrenoceptors. Dysfunction of the lower GI tract may increase noradrenaline release within the vBNST, which, in turn, may exacerbate impairment of its motility and pain perception.
• Sensitization of transient receptor potential vanilloid 4 and increasing its endogenous ligand 5,6-epoxyeicosatrienoic acid in rats with monoiodoacetate-induced osteoarthritis.
  Mikie Hinata; Sunao Imai; Takao Sanaki; Junji Tsuchida; Takeshi Yoshioka; Kenichi Higashino; Miyuki Yamamoto; Masayuki Imai; Masahiko Soga; Narumi Horita; Isao Fukuda; Minoru Ikeda; Shoji Yamane; Atsushi Morita; Toshiyuki Kanemasa; Gaku Sakaguchi; Minoru Hasegawa; Masabumi Minami; Yasuhide Morioka
  Pain, 159, 5, 939, 947, May 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Transient receptor potential vanilloid 4 (TRPV4) receptor modulates pain, and this has been noted in several animal models. However, the involvement of TRPV4 in osteoarthritic (OA) pain remains poorly understood. This study assessed the functional changes in TRPV4 and the expression of its endogenous ligand 5,6-epoxyeicosatrienoic acid (5,6-EET) in a rat monoiodoacetate (MIA)-induced OA pain model (MIA rats). Monoiodoacetate-treated rats showed reduced grip strength as compared to sham-treated rats, and this loss in function could be recovered by the intraarticular administration of a TRPV4 antagonist (HC067047 or GSK2193874). By contrast, the intraarticular administration of the TRPV4 agonist, GSK1016790A, increased the pain-related behaviors in MIA rats but not in sham rats. TRPV4 expression was not increased in knee joints of MIA rats; however, the levels of phosphorylated TRPV4 at Ser824 were increased in dorsal root ganglion neurons. In addition, 5,6-EET was increased in lavage fluids from the knee joints of MIA rats and in meniscectomy-induced OA pain model rats. 5,6-EET and its metabolite were also detected in synovial fluids from patients with OA. In conclusion, TRPV4 was sensitized in the knee joints of MIA rats through phosphorylation in dorsal root ganglion neurons, along with an increase in the levels of its endogenous ligand 5,6-EET. The analgesic effects of the TRPV4 antagonist in the OA pain model rats suggest that TRPV4 may be a potent target for OA pain relief.
• Pregabalin induces conditioned place preference in the rat during the early, but not late, stage of neuropathic pain
  Yuta Asaoka; Takahiro Kato; Soichiro Ide; Taiju Amano; Masabumi Minami
  Neuroscience Letters, 668, 133, 137, 06 Mar. 2018, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Bidirectional brain-gut interactions: Involvement of noradrenergic transmission within the ventral part of the bed nucleus of the stria terminalis.
  Ide S; Yamamoto R; Takeda H; Minami M
  Neuropsychopharmacology reports, 38, 1, 37, 43, Mar. 2018, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, Scientific journal, INTRODUCTION: Although the important roles of bidirectional interactions between the brain and gut in stress and emotional responses have long been recognized, the underlying neuronal mechanisms remain unclear. The bed nucleus of the stria terminalis (BNST) is a limbic structure involved in stress responses and negative affective states, such as anxiety and depression. We have previously demonstrated that noradrenergic transmission within the ventral part of the BNST (vBNST) plays a crucial role in anxiety-like behaviors and pain-induced aversion. OBJECTIVES: This study aimed to examine the involvement of noradrenergic transmission via β-adrenoceptors within the vBNST in bidirectional brain-gut interactions. METHODS: We measured the gastric distention (GD)-induced noradrenaline release within the vBNST of freely moving rats using an in vivo microdialysis technique. Gastric emptying and intestinal transit were examined following intra-vBNST injections of isoproterenol, a β-adrenoceptor agonist, in the absence or presence of the coadministration of timolol, a β-adrenoceptor antagonist. RESULTS: Gastric distention at a higher pressure (45 mm Hg) but not at a lower pressure (25 mm Hg) resulted in a significant increase in extracellular noradrenaline levels within the vBNST. Intra-vBNST injections of isoproterenol (30 nmol/side) induced significant reductions in gastric emptying and small intestinal transit, both of which were reversed by the coadministration of timolol (30 nmol/side). CONCLUSION: Noradrenergic transmission via β-adrenoceptors within the vBNST was involved in bidirectional brain-gut interactions. These findings suggest that gastric dysfunction may induce negative affective states via the enhanced release of noradrenaline within the vBNST which, in turn, may cause gastrointestinal impairments.
• Stress augments the rewarding memory of cocaine via the activation of brainstem-reward circuitry.
  Shinohara F; Asaoka Y; Kamii H; Minami M; Kaneda K
  Addiction biology, 24, 3, 509, 521, Feb. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Effects of stress on the reward system are well established in the literature. Although previous studies have revealed that stress can reinstate extinguished addictive behaviors related to cocaine, the effects of stress on the rewarding memory of cocaine are not fully understood. Here, we provide evidence that stress potentiates the expression of rewarding memory of cocaine via the activation of brainstem-reward circuitry using a cocaine-induced conditioned place preference (CPP) paradigm combined with restraint stress in rats. The rats exposed to 30-minute restraint stress immediately before posttest exhibited significantly larger CPP scores compared with non-stressed rats. Intra-laterodorsal tegmental nucleus (LDT) microinjection of a β or α2 adrenoceptor antagonist attenuated the stress-induced enhancement of cocaine CPP. Consistent with this observation, intra-LDT microinjection of a β or α2 adrenoceptor agonist before posttest increased cocaine CPP. Additionally, intra-ventral tegmental area (VTA) microinjection of antagonists for the muscarinic acetylcholine, nicotinic acetylcholine or glutamate receptors attenuated the stress-induced enhancement of cocaine CPP. Finally, intra-medial prefrontal cortex (mPFC) microinjection of a D1 receptor antagonist also reduced the stress-induced enhancement of cocaine CPP. These findings suggest a mechanism wherein the LDT is activated by noradrenergic input from the locus coeruleus, leading to the activation of VTA dopamine neurons via both cholinergic and glutamatergic transmission and the subsequent excitation of the mPFC to enhance the memory of cocaine-induced reward value.
• Astrocytic γ-aminobutyric acid (GABA) transporters mediate guanidinoacetate transport in rat brain
  Masanori Tachikawa; Ayane Yashiki; Shin-ichi Akanuma; Haruka Matsukawa; Soichiro Ide; Masabumi Minami; Ken-ichi Hosoya
  Neurochemistry International, 113, 1, 7, 01 Feb. 2018, [Peer-reviewed]
  English, Scientific journal
• Suppressive effects of morphine injected into the ventral bed nucleus of the stria terminalis on the affective, but not sensory, component of pain in rats
  Chikashi Maruyama; Satoshi Deyama; Yusuke Nagano; Soichiro Ide; Katsuyuki Kaneda; Mitsuhiro Yoshioka; Masabumi Minami
  European Journal of Neuroscience, 47, 1, 40, 47, 01 Jan. 2018, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Resolvin E3 attenuates lipopolysaccharide-induced depression-like behavior in mice
  Satoshi Deyama; Kento Shimoda; Hiroyuki Ikeda; Hayato Fukuda; Satoshi Shuto; Masabumi Minami
  Journal of Pharmacological Sciences, 138, 1, 86, 88, 2018, [Peer-reviewed], [Last author, Corresponding author]
• Resolvin E1/E2 ameliorate lipopolysaccharide-induced depression-like behaviors via ChemR23
  Satoshi Deyama; Kento Shimoda; Hiroe Suzuki; Yuka Ishikawa; Kohei Ishimura; Hayato Fukuda; Natsuko Hitora-Imamura; Soichiro Ide; Masamichi Satoh; Katsuyuki Kaneda; Satoshi Shuto; Masabumi Minami
  Psychopharmacology, 235, 1, 329, 336, 01 Jan. 2018, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Design and synthesis of cyclopropane-based conformationally restricted GABA analogues as selective inhibitors for betaine/GABA transporter 1
  Suemasa Akihiro; Watanabe Mizuki; Kobayashi Takaaki; Suzuki Hiroe; Fukuda Hayato; Minami Masabumi; Shuto Satoshi
  Bioorganic & Medicinal Chemistry Letters, 28, 20, 3395, 3399, 2018, [Peer-reviewed]
• Activation of the neural pathway from the dorsolateral bed nucleus of the stria terminalis to the central amygdala induces anxiety-like behaviors
  Naoki Yamauchi; Daiki Takahashi; Yae K Sugimura; Fusao Kato; Taiju Amano; Masabumi Minami
  European Journal of Neuroscience, 48, 9, 3052, 3061, 2018, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, Scientific journal
• The Role of Doparninergic Signaling in the Medial Prefrontal Cortex for the Expression of Cocaine-Induced Conditioned Place Preference in Rats
  Fumiya Shinohara; Hironori Kamii; Masabumi Minami; Katsuyuki Kaneda
  BIOLOGICAL & PHARMACEUTICAL BULLETIN, 40, 11, 1983, 1989, Nov. 2017, [Peer-reviewed]
  English, Scientific journal
• Nitric oxide in the medial prefrontal cortex contributes to the acquisition of cocaine place preference and synaptic plasticity in the laterodorsal tegmental nucleus
  Hironori Kamii; Naofumi Taoka; Masabumi Minami; Katsuyuki Kaneda
  NEUROSCIENCE LETTERS, 660, 39, 44, Nov. 2017, [Peer-reviewed]
  English, Scientific journal
• Rapid and sustained antidepressant effects of resolvin D1 and D2 in a chronic unpredictable stress model
  Yuka Ishikawa; Satoshi Deyama; Kento Shimoda; Kotomi Yoshikawa; Soichiro Ide; Masamichi Satoh; Masabumi Minami
  BEHAVIOURAL BRAIN RESEARCH, 332, 233, 236, Aug. 2017, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Resolvin D1 and D2 Reverse LipopolysaccharideInduced Depression-Like Behaviors Through the mTORC1 Signaling Pathway
  Satoshi Deyama; Yuka Ishikawa; Kotomi Yoshikawa; Kento Shimoda; Soichiro Ide; Masamichi Satoh; Masabumi Minami
  INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 20, 7, 575, 584, Jul. 2017, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Suppression of reward-induced dopamine release in the nucleus accumbens in animal models of depression: Differential responses to drug treatment
  Saki Minami; Hiroshi Satoyoshi; Soichiro Ide; Takeshi Inoue; Mitsuhiro Yoshioka; Masabumi Minami
  NEUROSCIENCE LETTERS, 650, 72, 76, May 2017, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Development-dependent behavioral change toward pups and synaptic transmission in the rhomboid nucleus of the bed nucleus of the stria terminalis
  Taiju Amano; Sayaka Shindo; Chihiro Yoshihara; Yousuke Tsuneoka; Haruka Uki; Masabumi Minami; Kumi O. Kuroda
  BEHAVIOURAL BRAIN RESEARCH, 325, 131, 137, May 2017, [Peer-reviewed]
  English, Scientific journal
• Activation of the NMDA receptor-neuronal nitric oxide synthase pathway within the ventral bed nucleus of the stria terminalis mediates the negative affective component of pain
  Satoshi Deyama; Yaya Sugano; Sakura Mori; Taiju Amano; Mitsuhiro Yoshioka; Katsuyuki Kaneda; Masabumi Minami
  NEUROPHARMACOLOGY, 118, 59, 68, May 2017, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Chronic cocaine exposure induces noradrenergic modulation of inhibitory synaptic transmission to cholinergic neurons of the laterodorsal tegmental nucleus
  Naofumi Taoka; Ryota Kamiizawa; Shintaro Wada; Masabumi Minami; Katsuyuki Kaneda
  EUROPEAN JOURNAL OF NEUROSCIENCE, 44, 12, 3035, 3045, Dec. 2016, [Peer-reviewed]
  English, Scientific journal
• Changes in glucose-induced plasma active glucagon-like peptide-1 levels by co-administration of sodium-glucose cotransporter inhibitors with dipeptidyl peptidase-4 inhibitors in rodents
  Takahiro Oguma; Chiaki Kuriyama; Keiko Nakayama; Yasuaki Matsushita; Kumiko Hikida; Minoru Tsuda-Tsukimoto; Akira Saito; Kenji Arakawa; Kiichiro Ueta; Masabumi Minami; Masaharu Shiotani
  JOURNAL OF PHARMACOLOGICAL SCIENCES, 132, 4, 255, 261, Dec. 2016, [Peer-reviewed]
  English, Scientific journal
• Activation of adenylate cyclase-cyclic AMP-protein kinase A signaling by corticotropin-releasing factor within the dorsolateral bed nucleus of the stria terminalis is involved in pain-induced aversion
  Tomoyuki Kaneko; Katsuyuki Kaneda; Atsushi Ohno; Daiki Takahashi; Taiki Hara; Taiju Amano; Soichiro Ide; Mitsuhiro Yoshioka; Masabumi Minami
  EUROPEAN JOURNAL OF NEUROSCIENCE, 44, 11, 2914, 2924, Dec. 2016, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Pain relief induces dopamine release in the rat nucleus accumbens during the early but not late phase of neuropathic pain
  Takahiro Kato; Soichiro Ide; Masabumi Minami
  NEUROSCIENCE LETTERS, 629, 73, 78, Aug. 2016, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Serotonin 5-HT7 Receptor in the Ventral Hippocampus Modulates the Retrieval of Fear Memory and Stress-Induced Defecation
  Yu Ohmura; Takayuki Yoshida; Kohtarou Konno; Masabumi Minami; Masahiko Watanabe; Mitsuhiro Yoshioka
  INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 19, 6, Jun. 2016, [Peer-reviewed]
  English, Scientific journal
• Amelioration of the reduced antinociceptive effect of morphine in the unpredictable chronic mild stress model mice by noradrenalin but not serotonin reuptake inhibitors
  Soichiro Ide; Hiroshi Satoyoshi; Masabumi Minami; Masamichi Satoh
  MOLECULAR PAIN, 11, Aug. 2015, [Peer-reviewed]
  English, Scientific journal
• Corticotropin-releasing factor enhances inhibitory synaptic transmission to type III neurons in the bed nucleus of the stria terminalis
  Yusuke Nagano; Katsuyuki Kaneda; Chikashi Maruyama; Soichiro Ide; Fusao Kato; Masabumi Minami
  NEUROSCIENCE LETTERS, 600, 56, 61, Jul. 2015, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Intrinsic membrane plasticity via increased persistent sodium conductance of cholinergic neurons in the rat laterodorsal tegmental nucleus contributes to cocaine-induced addictive behavior
  Hironori Kamii; Ryo Kurosawa; Naofumi Taoka; Fumiya Shinohara; Masabumi Minami; Katsuyuki Kaneda
  EUROPEAN JOURNAL OF NEUROSCIENCE, 41, 9, 1126, 1138, May 2015, [Peer-reviewed]
  English, Scientific journal
• How Does Pain Induce Negative Emotion? Role of the Bed Nucleus of the Stria Terminalis in Pain-Induced Place Aversion
  M. Minami; S. Ide
  CURRENT MOLECULAR MEDICINE, 15, 2, 184, 190, 2015, [Peer-reviewed]
  English, Scientific journal
• Haplotypes of P2RX7 gene polymorphisms are associated with both cold pain sensitivity and analgesic effect of fentanyl
  Soichiro Ide; Daisuke Nishizawa; Ken-ichi Fukuda; Shinya Kasai; Junko Hasegawa; Masakazu Hayashida; Masabumi Minami; Kazutaka Ikeda
  MOLECULAR PAIN, 10, Dec. 2014, [Peer-reviewed]
  English, Scientific journal
• Conformationally restricted GABA with bicyclo[3.1.0]hexane backbone as the first highly selective BGT-1 inhibitor
  Takaaki Kobayashi; Akihiro Suemasa; Arisa Igawa; Soichiro Ide; Hayato Fukuda; Hiroshi Abe; Mitsuhiro Arisawa; Masabumi Minami; Satoshi Shuto
  ACS Medicinal Chemistry Letters, 5, 8, 889, 893, 14 Aug. 2014, [Peer-reviewed]
  Scientific journal
• GABAergic neurons in the ventral tegmental area receive dual GABA/enkephalin-mediated inhibitory inputs from the bed nucleus of the stria terminalis
  Takehiro Kudo; Kohtarou Konno; Motokazu Uchigashima; Yuchio Yanagawa; Ichiro Sora; Masabumi Minami; Masahiko Watanabe
  EUROPEAN JOURNAL OF NEUROSCIENCE, 39, 11, 1796, 1809, Jun. 2014, [Peer-reviewed]
  English, Scientific journal
• Critical role of cholinergic transmission from the laterodorsal tegmental nucleus to the ventral tegmental area in cocaine-induced place preference
  Fumiya Shinohara; Yukari Kihara; Soichiro Ide; Masabumi Minami; Katsuyuki Kaneda
  NEUROPHARMACOLOGY, 79, 573, 579, Apr. 2014, [Peer-reviewed]
  English, Scientific journal
• SYNTHESIS OF 4-ARYLPIPERIDIN-4-OL DERIVATIVES OF LOPERAMIDE AS AGENTS WITH POTENT ANTIPROLIFERATIVE EFFECTS AGAINST HCT-116 AND HL-60 CELLS
  Noriyuki Hatae; Tomoyuki Nagayama; Hiroyoshi Esaki; Eiko Kujime; Masabumi Minami; Minoru Ishikura; Tominari Choshi; Satoshi Hibino; Chiaki Okada; Eiko Toyota; Hideko Nagasawa; Tatsunori Iwamura
  HETEROCYCLES, 88, 1, 663, 673, Jan. 2014, [Peer-reviewed]
  English, Scientific journal
• Cocaine exposure enhances excitatory synaptic drive to cholinergic neurons in the laterodorsal tegmental nucleus
  Ryo Kurosawa; Naofumi Taoka; Fumiya Shinohara; Masabumi Minami; Katsuyuki Kaneda
  EUROPEAN JOURNAL OF NEUROSCIENCE, 38, 7, 3027, 3035, Oct. 2013, [Peer-reviewed]
  English, Scientific journal
• Cyclopropane-based conformational restriction of GABA by a stereochemical diversity-oriented strategy: Identification of an efficient lead for potent inhibitors of GABA transports
  Kazuaki Nakada; Mamie Yoshikawa; Soichiro Ide; Akihiro Suemasa; Shuhei Kawamura; Takaaki Kobayashi; Eiji Masuda; Yoshihiko Ito; Wataru Hayakawa; Takahiro Katayama; Shizuo Yamada; Mitsuhiro Arisawa; Masabumi Minami; Satoshi Shuto
  Bioorganic and Medicinal Chemistry, 21, 17, 4938, 4950, 01 Sep. 2013, [Peer-reviewed]
  Scientific journal
• Association between Genetic Polymorphisms in Ca(v)2.3 (R-type) Ca2+ Channels and Fentanyl Sensitivity in Patients Undergoing Painful Cosmetic Surgery
  Soichiro Ide; Daisuke Nishizawa; Ken-ichi Fukuda; Shinya Kasai; Junko Hasegawa; Masakazu Hayashida; Masabumi Minami; Kazutaka Ikeda
  PLOS ONE, 8, 8, e70694, Aug. 2013, [Peer-reviewed]
  English, Scientific journal
• Tandospirone Suppresses Impulsive Action by Possible Blockade of the 5-HT1A Receptor
  Yu Ohmura; Haruko Kumamoto; Iku Tsutsui-Kimura; Masabumi Minami; Takeshi Izumi; Takayuki Yoshida; Mitsuhiro Yoshioka
  JOURNAL OF PHARMACOLOGICAL SCIENCES, 122, 2, 84, 92, Jun. 2013, [Peer-reviewed]
  English, Scientific journal
• Opposing Roles of Corticotropin-Releasing Factor and Neuropeptide Y within the Dorsolateral Bed Nucleus of the Stria Terminalis in the Negative Affective Component of Pain in Rats
  Soichiro Ide; Taiki Hara; Atsushi Ohno; Ryuta Tamano; Kana Koseki; Tomonori Naka; Chikashi Maruyama; Katsuyuki Kaneda; Mitsuhiro Yoshioka; Masabumi Minami
  JOURNAL OF NEUROSCIENCE, 33, 14, 5881, 5894, Apr. 2013, [Peer-reviewed]
  English, Scientific journal
• Activation of β-adrenoceptors in the bed nucleus of the stria terminalis induces food intake reduction and anxiety-like behaviors
  Tomonori Naka; Soichiro Ide; Tomokazu Nakako; Mikie Hirata; Yuki Majima; Satoshi Deyama; Hiroshi Takeda; Mitsuhiro Yoshioka; Masabumi Minami
  Neuropharmacology, 67, 326, 330, Apr. 2013, [Peer-reviewed]
  English, Scientific journal
• Addition of Cyclic Ureas and 1-Methyl-2-oxazolidone to Pyridynes: A New Approach to Pyridodiazepines, Pyridodiazocines, and Pyridooxazepines
  Nozomi Saito; Ken-ichi Nakamura; Sayako Shibano; Soichiro Ide; Masabumi Minami; Yoshihiro Sato
  ORGANIC LETTERS, 15, 2, 386, 389, Jan. 2013, [Peer-reviewed]
  English, Scientific journal
• Three Types of Neurochemical Projection from the Bed Nucleus of the Stria Terminalis to the Ventral Tegmental Area in Adult Mice
  Takehiro Kudo; Motokazu Uchigashima; Taisuke Miyazaki; Kohtarou Konno; Miwako Yamasaki; Yuchio Yanagawa; Masabumi Minami; Masahiko Watanabe
  JOURNAL OF NEUROSCIENCE, 32, 50, 18035, 18046, Dec. 2012, [Peer-reviewed]
  English, Scientific journal
• Neuronal injury induces microglial production of macrophage inflammatory protein-1a in rat corticostriatal slice cultures
  Toshiyuki Okamura; Takahiro Katayama; Chihiro Obinata; Yukina Iso; Yuzuho Chiba; Hayato Kobayashi; Yuma Yamada; Hideyoshi Harashima; Masabumi Minami
  JOURNAL OF NEUROSCIENCE RESEARCH, 90, 11, 2127, 2133, Nov. 2012, [Peer-reviewed]
  English, Scientific journal
• Accumulating Microglia Phagocytose Injured Neurons in Hippocampal Slice Cultures: Involvement of p38 MAP Kinase
  Takahiro Katayama; Hayato Kobayashi; Toshiyuki Okamura; Yuko Yamasaki-Katayama; Tatsuya Kibayashi; Hiroshi Kimura; Keiko Ohsawa; Shinichi Kohsaka; Masabumi Minami
  PLOS ONE, 7, 7, Jul. 2012, [Peer-reviewed]
  English, Scientific journal
• Nicotine- and Tar-Free Cigarette Smoke Induces Cell Damage Through Reactive Oxygen Species Newly Generated by PKC-Dependent Activation of NADPH Oxidase
  Hiroshi Asano; Takahiro Horinouchi; Yosuke Mai; Osamu Sawada; Shunsuke Fujii; Tadashi Nishiya; Masabumi Minami; Takahiro Katayama; Toshihiko Iwanaga; Koji Terada; Soichi Miwa
  JOURNAL OF PHARMACOLOGICAL SCIENCES, 118, 2, 275, 287, Feb. 2012, [Peer-reviewed]
  English, Scientific journal
• Lithium, but not valproic acid or carbamazepine, suppresses impulsive-like action in rats
  Yu Ohmura; Iku Tsutsui-Kimura; Haruko Kumamoto; Masabumi Minami; Takeshi Izumi; Taku Yamaguchi; Takayuki Yoshida; Mitsuhiro Yoshioka
  PSYCHOPHARMACOLOGY, 219, 2, 421, 432, Jan. 2012, [Peer-reviewed]
  English, Scientific journal
• Mesenchymal stem cells transmigrate across brain microvascular endothelial cell monolayers through transiently formed inter-endothelial gaps
  Takashi Matsushita; Tatsuya Kibayashi; Takahiro Katayama; Yuuki Yamashita; Syuuichirou Suzuki; Jun Kawamata; Osamu Honmou; Masabumi Minami; Shun Shimohama
  NEUROSCIENCE LETTERS, 502, 1, 41, 45, Sep. 2011, [Peer-reviewed]
  English, Scientific journal
• Inhibition of noradrenaline release by clonidine in the ventral bed nucleus of the stria terminalis attenuates pain-induced aversion in rats
  Satoshi Deyama; Soichiro Ide; Naoto Kondoh; Taku Yamaguchi; Mitsuhiro Yoshioka; Masabumi Minami
  NEUROPHARMACOLOGY, 61, 1-2, 156, 160, Jul. 2011, [Peer-reviewed]
  English, Scientific journal
• On-off system for PI3-kinase-Akt signaling through S-nitrosylation of phosphatase with sequence homology to tensin (PTEN)
  Naoki Numajiri; Kumi Takasawa; Tadashi Nishiya; Hirotaka Tanaka; Kazuki Ohno; Wataru Hayakawa; Mariko Asada; Hiromi Matsuda; Kaoru Azumi; Hideaki Kamata; Tomohiro Nakamura; Hideaki Hara; Masabumi Minami; Stuart A. Lipton; Takashi Uehara
  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 108, 25, 10349, 10354, Jun. 2011, [Peer-reviewed]
  English, Scientific journal
• (-)-Pentazocine induces visceral chemical antinociception, but not thermal, mechanical, or somatic chemical antinociception, in mu-opioid receptor knockout mice
  Soichiro Ide; Masabumi Minami; George R. Uhl; Masamichi Satoh; Ichiro Sora; Kazutaka Ikeda
  MOLECULAR PAIN, 7, Apr. 2011, [Peer-reviewed]
  English, Scientific journal
• Neurochemical characterization of neurons in the bed nucleus of the stria terminalis projecting to the ventral tegmental area
  Kudo Takehiro; Uchigashima Motokazu; Miyazaki Taisuke; Yamasaki Miwako; Minami Masabumi; Watanabe Masahiko
  NEUROSCIENCE RESEARCH, 71, E322, 2011, [Peer-reviewed]
• Roles of beta- and alpha(2)-Adrenoceptors Within the Central Nucleus of the Amygdala in the Visceral Pain-Induced Aversion in Rats
  Satoshi Deyama; Azusa Takishita; Sachi Tanimoto; Soichiro Ide; Takayuki Nakagawa; Masamichi Satoh; Masabumi Minami
  JOURNAL OF PHARMACOLOGICAL SCIENCES, 114, 1, 123, 126, Sep. 2010, [Peer-reviewed]
  English, Scientific journal
• Antidepressant-Like Effect of Venlafaxine Is Abolished in mu-Opioid Receptor-Knockout Mice
  Soichiro Ide; Shunsuke Fujiwara; Masayuki Fujiwara; Ichiro Sora; Kazutaka Ikeda; Masabumi Minami; George R. Uhl; Kumatoshi Ishihara
  JOURNAL OF PHARMACOLOGICAL SCIENCES, 114, 1, 107, 110, Sep. 2010, [Peer-reviewed]
  English, Scientific journal
• Sustained activation of ERK signaling in astrocytes is critical for neuronal injury-induced monocyte chemoattractant protein-1 production in rat corticostriatal slice cultures
  Takahiro Katayama; Emi Sakaguchi; Yosuke Komatsu; Takahiro Oguma; Takashi Uehara; Masabumi Minami
  EUROPEAN JOURNAL OF NEUROSCIENCE, 31, 8, 1359, 1367, Apr. 2010, [Peer-reviewed]
  English, Scientific journal
• Combination of cell culture assays and knockout mouse analyses for the study of opioid partial agonism.
  Ide S; Minami M; Sora I; Ikeda K
  Methods in molecular biology (Clifton, N.J.), 617, 363, 374, 2010, [Peer-reviewed]
• Reduced emotional and corticosterone responses to stress in mu-opioid receptor knockout mice
  Soichiro Ide; Ichiro Sora; Kazutaka Ikeda; Masabumi Minami; George R. Uhl; Kumatoshi Ishihara
  NEUROPHARMACOLOGY, 58, 1, 241, 247, Jan. 2010, [Peer-reviewed]
  English, Scientific journal
• Reciprocal Regulation of ATP gamma S-induced Monocyte Chemoattractant Protein-1 Production by ERK and p38 MAP Kinases in Rat Corticostriatal Slice Cultures
  Takahiro Katayama; Misato Ito; Shuji Kaneko; Masamichi Satoh; Takashi Uehara; Masabumi Minami
  JOURNAL OF NEUROSCIENCE RESEARCH, 87, 7, 1573, 1581, May 2009, [Peer-reviewed]
  English, Scientific journal
• Role of enhanced noradrenergic transmission within the ventral bed nucleus of the stria terminalis in visceral pain-induced aversion in rats
  Satoshi Deyama; Takahiro Katayama; Naoto Kondoh; Takayuki Nakagawa; Shuji Kaneko; Taku Yamaguchi; Mitsuhiro Yoshioka; Masabumi Minami
  BEHAVIOURAL BRAIN RESEARCH, 197, 2, 279, 283, Feb. 2009, [Peer-reviewed]
  English, Scientific journal
• Neuronal Injury Induces Cytokine-Induced Neutrophil Chemoattractant-1 (CINC-1) Production in Astrocytes
  Takahiro Katayama; Hiroki Tanaka; Tadashi Yoshida; Takashi Uehara; Masabumi Minami
  JOURNAL OF PHARMACOLOGICAL SCIENCES, 109, 1, 88, 93, Jan. 2009, [Peer-reviewed]
  English, Scientific journal
• NEURONAL MECHANISMS FOR PAIN-INDUCED AVERSION: BEHAVIORAL STUDIES USING A CONDITIONED PLACE AVERSION TEST
  Masabumi Minami
  ADVANCES IN NEUROPHARMACOLOGY, 85, 135, 144, 2009, [Peer-reviewed]
  English
• Activation of the beta-adrenoceptor-protein kinase A signaling pathway within the ventral bed nucleus of the stria terminalis mediates the negative affective component of pain in rats
  Satoshi Deyama; Takahiro Katayama; Atsushi Ohno; Takayuki Nakagawa; Shuji Kaneko; Taku Yamaguchi; Mitsuhiro Yoshioka; Masabumi Minami
  JOURNAL OF NEUROSCIENCE, 28, 31, 7728, 7736, Jul. 2008, [Peer-reviewed]
  English, Scientific journal
• Abolished thermal and mechanical antinociception but retained visceral chemical antinociception induced by butorphanol in mu-opioid receptor knockout mice
  Soichiro Ide; Masabumi Minami; Kumatoshi Ishihara; George R. Uhl; Masamichi Satoh; Ichiro Sora; Kazutaka Ikeda
  NEUROPHARMACOLOGY, 54, 8, 1182, 1188, Jun. 2008, [Peer-reviewed]
  English, Scientific journal
• Inhibition of glutamatergic transmission by morphine in the basolateral amygdaloid nucleus reduces pain-induced aversion
  Satoshi Deyama; Junki Yamamoto; Taiichi Machida; Sachi TaniMoto; Takayuki Nakagawa; Shuji Kaneko; Masamichi Satoh; Masabumi Minami
  NEUROSCIENCE RESEARCH, 59, 2, 199, 204, Oct. 2007, [Peer-reviewed]
  English, Scientific journal
• Intrathecal administration of atp produces long-lasting allodynia in rats: Differential mechanisms in the phase of the induction and maintenance
  T. Nakagawa; K. Wakamatsu; N. Zhang; S. Maeda; M. Minami; M. Satoh; S. Kaneko
  NEUROSCIENCE, 147, 2, 445, 455, Jun. 2007, [Peer-reviewed]
  English, Scientific journal
• Involvement of the bed nucleus of the stria terminalis in the negative affective component of visceral and somatic pain in rats
  Satoshi Deyama; Takayuki Nakagawa; Shuji Kaneko; Takashi Uehara; Masabumi Minami
  BEHAVIOURAL BRAIN RESEARCH, 176, 2, 367, 371, Jan. 2007, [Peer-reviewed]
  English, Scientific journal
• Mu opioid receptor-dependent and independent components in effects of tramadol
  Soichiro Ide; Masabumi Minami; Kumatoshi Ishihara; George R. Uhl; Ichiro Sora; Kazutaka Ikeda
  NEUROPHARMACOLOGY, 51, 3, 651, 658, Sep. 2006, [Peer-reviewed]
  English, Scientific journal
• Inhibitory role of supraspinal P2X(3)/P2X(2/3) subtypes on nociception in rats
  Masato Fukui; Takayuki Nakagawa; Masabumi Minami; Masamichi Satoh; Shuji Kaneko
  MOLECULAR PAIN, 2, Jun. 2006, [Peer-reviewed]
  English, Scientific journal
• Linkage disequilibrium and association with methamphetamine dependence/psychosis of mu-opioid receptor gene polymorphisms
  S. Ide; H. Kobayashi; H. Ujike; N. Ozaki; Y. Sekine; T. Inada; M. Harano; T. Komiyama; M. Yamada; M. Iyo; N. Iwata; K. Tanaka; H. Shen; K. Iwahashi; M. Itokawa; M. Minami; M. Satoh; K. Ikeda; I. Sora
  PHARMACOGENOMICS JOURNAL, 6, 3, 179, 188, May 2006, [Peer-reviewed]
  English, Scientific journal
• Glucocorticoid modulatory element-binding protein 1 binds to initiator procaspases and inhibits ischemia-induced apoptosis and neuronal injury
  K Tsuruma; T Nakagawa; N Morimoto; M Minami; H Hara; T Uehara; Y Nomura
  JOURNAL OF BIOLOGICAL CHEMISTRY, 281, 16, 11397, 11404, Apr. 2006, [Peer-reviewed]
  English, Scientific journal
• Brain cytokines and chemokines: Roles in ischemic injury and pain
  M Minami; T Katayama; M Satoh
  JOURNAL OF PHARMACOLOGICAL SCIENCES, 100, 5, 461, 470, 2006, [Peer-reviewed]
  English
• Gene transfer of GLT-1, a glutamate transporter, into the nucleus accumbens shell attenuates methamphetamine- and morphine-induced conditioned place preference in rats
  M Fujio; T Nakagawa; Y Sekiya; T Ozawa; Y Suzuki; M Minami; M Satoh; S Kaneko
  EUROPEAN JOURNAL OF NEUROSCIENCE, 22, 11, 2744, 2754, Dec. 2005, [Peer-reviewed]
  English, Scientific journal
• Activation of astrocytes by NMDA-induced neuronal injury
  Masabumi Minami; Takahiro Katayama; Masamichi Satoh
  YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 125, 57, 60, 2005, [Peer-reviewed]
  Japanese, Scientific journal
• Effects of MS-153, a glutamate transporter activator, on the conditioned rewarding effects of morphine, methamphetamine and cocaine in mice
  T Nakagawa; M Fujio; T Ozawa; M Minami; M Satoh
  BEHAVIOURAL BRAIN RESEARCH, 156, 2, 233, 239, Jan. 2005, [Peer-reviewed]
  English, Scientific journal
• Role of chemokines in ischemic neuronal stress
  M Minami; M Satoh
  NEUROMOLECULAR MEDICINE, 7, 1-2, 149, 155, 2005, [Peer-reviewed]
  English, Scientific journal
• Involvement of the bed nucleus of the stria terminalis activated by the central nucleus of the amygdala in the negative affective component of morphine withdrawal in rats
  T Nakagawa; R Yamamoto; M Fujio; Y Suzuki; M Minami; M Satoh; S Kaneko
  NEUROSCIENCE, 134, 1, 9, 19, 2005, [Peer-reviewed]
  English, Scientific journal
• Buprenorphine antinociception is abolished, but naloxone-sensitive reward is retained, in mu-opioid receptor knockout mice
  S Ide; M Minami; M Satoh; GR Uhl; Sora, I; K Ikeda
  NEUROPSYCHOPHARMACOLOGY, 29, 9, 1656, 1663, Sep. 2004, [Peer-reviewed]
  English, Scientific journal
• Dual-gene, dual-cell type therapy against an excitotoxic insult by bolstering neuroenergetics
  TM Bliss; M Ip; E Cheng; M Minami; L Pellerin; P Magistretti; RM Sapolsky
  JOURNAL OF NEUROSCIENCE, 24, 27, 6202, 6208, Jul. 2004, [Peer-reviewed]
  English, Scientific journal
• Enhanced production of monocyte chemoattractant protein-1 in the dorsal root ganglia in a rat model of neuropathic pain: possible involvement in the development of neuropathic pain
  T Tanaka; M Minami; T Nakagawa; M Satoh
  NEUROSCIENCE RESEARCH, 48, 4, 463, 469, Apr. 2004, [Peer-reviewed]
  English, Scientific journal
• Facilitation of morphine withdrawal symptoms and morphine-induced conditioned place preference by a glutamate transporter inhibitor DL-threo-beta-benzyloxyaspartate in rats
  Y Sekiya; T Nakagawa; T Ozawa; M Minami; M Satoh
  EUROPEAN JOURNAL OF PHARMACOLOGY, 485, 1-3, 201, 210, Feb. 2004, [Peer-reviewed]
  English, Scientific journal
• Involvement of locus coeruleus noradrenergic neurons in supraspinal antinociception by alpha,beta-methylene-ATP in rats
  M Fukui; A Takishita; NN Zhang; T Nakagawa; M Minami; M Satoh
  JOURNAL OF PHARMACOLOGICAL SCIENCES, 94, 2, 153, 160, Feb. 2004, [Peer-reviewed]
  English, Scientific journal
• Molecular pharmacology of opioid receptors
  Masabumi Minami
  Folia Pharmacologica Japonica, 123, 2, 95, 104, 2004, [Peer-reviewed]
  Japanese, International conference proceedings
• Effect of gene transfer of GLT-1, a glutamate transporter, into the locus coeruleus by recombinant adenoviruses on morphine physical dependence in rats
  T Ozawa; T Nakagawa; Y Sekiya; M Minami; M Satoh
  EUROPEAN JOURNAL OF NEUROSCIENCE, 19, 1, 221, 226, Jan. 2004, [Peer-reviewed]
  English, Scientific journal
• Chemokines and their receptors in the brain: Pathophysiological roles in ischemic brain injury
  M Minami; M Satoh
  LIFE SCIENCES, 74, 2-3, 321, 327, Dec. 2003, [Peer-reviewed]
  English, Scientific journal
• Involvement of noradrenergic system within the central nucleus of the amygdala in naloxone-precipitated morphine withdrawal-induced conditioned place aversion in rats
  T Watanabe; T Nakagawa; R Yamamoto; A Maeda; M Minami; M Satoh
  PSYCHOPHARMACOLOGY, 170, 1, 80, 88, Oct. 2003, [Peer-reviewed]
  English, Scientific journal
• Differential contributions of the basolateral and central nuclei of the amygdala in the negative affective component of chemical somatic and visceral pains in rats
  S Tanimoto; T Nakagawa; Y Yamauchi; M Minami; M Satoh
  EUROPEAN JOURNAL OF NEUROSCIENCE, 18, 8, 2343, 2350, Oct. 2003, [Peer-reviewed]
  English, Scientific journal
• Differential patterns of c-fos mRNA expression in the amygdaloid nuclei induced by chemical somatic and visceral noxious stimuli in rats
  T Nakagawa; A Katsuya; S Tanimoto; J Yamamoto; Y Yamauchi; M Minami; M Satoh
  NEUROSCIENCE LETTERS, 344, 3, 197, 200, Jul. 2003, [Peer-reviewed]
  English, Scientific journal
• Supraspinal antinociception by intracerebroventricular administration of P2 purinoceptor agonists in rats
  Fukui, M; Takishita, A; Zhang, N; Nakagawa, T; Minami, M; Satoh, M
  Pain Res, 18, 115, 120, 2003, [Peer-reviewed], [Invited]
  Japanese, Scientific journal
• Effects of excitotoxic lesions of the central or basolateral nucleus of the amygdala on naloxone-precipitated withdrawal-induced conditioned place aversion in morphine-dependent rats
  T Watanabe; R Yamamoto; A Maeda; T Nakagawa; M Minami; M Satoh
  BRAIN RESEARCH, 958, 2, 423, 428, Dec. 2002, [Peer-reviewed]
  English, Scientific journal
• Antagonism of NMDA receptors by sigma receptor ligands attenuates chemical ischemia-induced neuronal death in vitro
  T Kume; H Nishikawa; R Taguchi; A Hashino; H Katsuki; S Kaneko; M Minami; M Satoh; A Akaike
  EUROPEAN JOURNAL OF PHARMACOLOGY, 455, 2-3, 91, 100, Nov. 2002, [Peer-reviewed]
  English, Scientific journal
• Kainic acid induces leukemia inhibitory factor mRNA expression in the rat brain: differences in the time course of mRNA expression between the dentate gyrus and hippocampal CA1/CA3 subfields
  M Minami; K Maekawa; H Yamakuni; T Katayama; J Nakamura; M Satoh
  MOLECULAR BRAIN RESEARCH, 107, 1, 39, 46, Oct. 2002, [Peer-reviewed]
  English, Scientific journal
• Analgesic effects of intrathecal administration of P2Y nucleotide receptor agonists UTP and UDP in normal and neuropathic pain model rats
  M Okada; T Nakagawa; M Minami; M Satoh
  JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 303, 1, 66, 73, Oct. 2002, [Peer-reviewed]
  English, Scientific journal
• Excitotoxic injury induces production of monocyte chemoattractant protein-1 in rat cortico-striatal slice cultures
  T Katayama; M Minami; M Nakamura; M Ito; H Katsuki; A Akaike; M Satoh
  NEUROSCIENCE LETTERS, 328, 3, 277, 280, Aug. 2002, [Peer-reviewed]
  English, Scientific journal
• ATP induces leukemia inhibitory factor mRNA in cultured rat astrocytes
  H Yamakuni; N Kawaguchi; Y Ohtani; J Nakamura; T Katayama; T Nakagawa; M Minami; M Satoh
  JOURNAL OF NEUROIMMUNOLOGY, 129, 1-2, 43, 50, Aug. 2002, [Peer-reviewed]
  English, Scientific journal
• TAK-779, a nonpeptide CC chemokine receptor antagonist, protects the brain against focal cerebral ischemia in mice
  S Takami; M Minami; T Katayama; Nagata, I; S Namura; M Satoh
  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 22, 7, 780, 784, Jul. 2002, [Peer-reviewed]
  English, Scientific journal
• Involvement of glutamate receptors within the central nucleus of the amygdala in naloxone-precipitated morphine withdrawal-induced conditioned place aversion in rats
  T Watanabe; T Nakagawa; R Yamamoto; A Maeda; M Minami; M Satoh
  JAPANESE JOURNAL OF PHARMACOLOGY, 88, 4, 399, 406, Apr. 2002, [Peer-reviewed]
  English, Scientific journal
• Behavioural and pharmacological relevance of stroke-prone spontaneously hypertensive rats as an animal model of a developmental disorder
  K Ueno; H Togashi; K Mori; M Matsumoto; S Ohashi; A Hoshino; T Fujita; H Saito; M Minami; M Yoshioka
  BEHAVIOURAL PHARMACOLOGY, 13, 1, 1, 13, Feb. 2002, [Peer-reviewed]
  English, Scientific journal
• Up-regulation of RGS4 mRNA by opioid receptor agonists in PC12 cells expressing cloned mu- or kappa-opioid receptors
  T Nakagawa; M Minami; M Satoh
  EUROPEAN JOURNAL OF PHARMACOLOGY, 433, 1, 29, 36, Dec. 2001, [Peer-reviewed]
  English, Scientific journal
• Chemokine receptor antagonist peptide, viral MIP-II, protects the brain against focal cerebral ischemia in mice
  S Takami; M Minami; T Nagata; T Namura; M Satoh
  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 21, 12, 1430, 1435, Dec. 2001, [Peer-reviewed]
  English, Scientific journal
• Leukemia inhibitory factor induces nociceptin mRNA in cultured rat cortical neurons
  M Minami; H Yamakuni; Y Ohtani; M Okada; J Nakamura; M Satoh
  NEUROSCIENCE LETTERS, 311, 1, 17, 20, Sep. 2001, [Peer-reviewed]
  English, Scientific journal
• Involvement of beta(2)-adrenergic and mu-opioid receptors in antinociception produced by intracerebroventricular administration of alpha,beta-methylene-ATP
  M Fukui; T Nakagawa; M Minami; M Satoh
  JAPANESE JOURNAL OF PHARMACOLOGY, 86, 4, 423, 428, Aug. 2001, [Peer-reviewed]
  English, Scientific journal
• Changes in the expression of glial glutamate transporters in the rat brain accompanied with morphine dependence and naloxone-precipitated withdrawal
  T Ozawa; T Nakagawa; K Shige; M Minami; M Satoh
  BRAIN RESEARCH, 905, 1-2, 254, 258, Jun. 2001, [Peer-reviewed]
  English, Scientific journal
• Antinociceptive effects of intracerebroventricularly administered P2 purinoceptor agonists in the rat
  M Fukui; T Nakagawa; M Minami; M Satoh
  EUROPEAN JOURNAL OF PHARMACOLOGY, 419, 1, 25, 31, May 2001, [Peer-reviewed]
  English, Scientific journal
• Inhibition of morphine tolerance and dependence by MS-153, a glutamate transporter activator
  T Nakagawa; T Ozawa; K Shige; R Yamamoto; M Minami; M Satoh
  EUROPEAN JOURNAL OF PHARMACOLOGY, 419, 1, 39, 45, May 2001, [Peer-reviewed]
  English, Scientific journal
• Calbindin D28K overexpression protects striatal neurons from transient focal cerebral ischemia
  MA Yenari; M Minami; GH Sun; TJ Meier; DM Kunis; McLaughlin, JR; DY Ho; RM Sapolsky; GK Steinberg
  STROKE, 32, 4, 1028, 1035, Apr. 2001, [Peer-reviewed]
  English, Scientific journal
• Expression of inducible nitric oxide synthase mRNA and production of nitric oxide are induced by adenosine triphosphate in cultured rat microglia
  Y Ohtani; M Minami; M Satoh
  NEUROSCIENCE LETTERS, 293, 1, 72, 74, Oct. 2000, [Peer-reviewed]
  English, Scientific journal
• Endomorphin-1 discriminates the mu-opioid receptor from the delta- and kappa-opioid receptors by recognizing the difference in multiple regions
  S Ide; K Sakano; T Seki; S Awamura; M Minami; M Satoh
  JAPANESE JOURNAL OF PHARMACOLOGY, 83, 4, 306, 311, Aug. 2000, [Peer-reviewed]
  English, Scientific journal
• 【最先端創薬】 先端的医薬品 単一成分に対するアプローチ 受容体 オピオイド受容体
  佐藤 公道; 関 貴弘; 南 雅文
  蛋白質・核酸・酵素, 45, 6, 985, 990, 共立出版(株), Apr. 2000
  Japanese
• Localization of calcitonin receptor mRNA in the mouse brain: coexistence with serotonin transporter mRNA
  H Nakamoto; Y Soeda; S Takami; M Minami; M Satoh
  MOLECULAR BRAIN RESEARCH, 76, 1, 93, 102, Mar. 2000, [Peer-reviewed]
  English, Scientific journal
• Possible involvement of the locus coeruleus in inhibition by prostanoid EP3 receptor-selective agonists of morphine withdrawal syndrome in rats
  T Nakagawa; T Masuda; T Watanabe; M Minami; M Satoh
  EUROPEAN JOURNAL OF PHARMACOLOGY, 390, 3, 257, 266, Mar. 2000, [Peer-reviewed]
  English, Scientific journal
• Opioid receptors
  M. Satoh; T. Seki; M. Minami
  Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme, 45, 6 Suppl, 985, 990, 01 Jan. 2000
• Sensitization of the adenylyl cyclase system in cloned kappa-opioid receptor-transfected cells following sustained agonist treatment: A chimeric study using G protein alpha(i2)/alpha(q) subunits
  T Nakagawa; T Ozawa; T Watanabe; M Minami; M Satoh
  JAPANESE JOURNAL OF PHARMACOLOGY, 81, 4, 353, 361, Dec. 1999, [Peer-reviewed]
  English, Scientific journal
• Pharmacological properties of TRK-820 on cloned mu-, delta- and kappa-opioid receptors and nociceptin receptor
  T Seki; S Awamura; C Kimura; S Ide; K Sakano; M Minami; H Nagase; M Satoh
  EUROPEAN JOURNAL OF PHARMACOLOGY, 376, 1-2, 159, 167, Jul. 1999, [Peer-reviewed]
  English, Scientific journal
• Supersensitization of the adenylyl cyclase system in Chinese hamster ovary cells co-expressing cloned opioid receptors and G(z), a PTX-insensitive G protein
  T Ozawa; T Nakagawa; M Minami; M Satoh
  NEUROSCIENCE LETTERS, 267, 2, 117, 120, May 1999, [Peer-reviewed]
  English, Scientific journal
• Apoptotic DNA fragmentation and upregulation of Bax induced by transient ischemia of the rat retina
  K Kaneda; S Kashii; T Kurosawa; S Kaneko; A Akaike; Y Honda; M Minami; M Satoh
  BRAIN RESEARCH, 815, 1, 11, 20, Jan. 1999, [Peer-reviewed]
  English, Scientific journal
• A hyperalgesic effect of intracerebroventricular cytokine-induced neutrophil chemoattractant-1 in the rat paw pressure test
  J Yamamoto; A Nishiyori; S Takami; Y Ohtani; M Minami; M Satoh
  EUROPEAN JOURNAL OF PHARMACOLOGY, 363, 2-3, 131, 133, Dec. 1998, [Peer-reviewed]
  English, Scientific journal
• Bremazocine recognizes the difference in four amino acid residues to discriminate between a nociceptin/orphanin FQ receptor and opioid receptors
  T Seki; M Minami; C Kimura; T Uehara; T Nakagawa; M Satoh
  JAPANESE JOURNAL OF PHARMACOLOGY, 77, 4, 301, 306, Aug. 1998, [Peer-reviewed]
  English, Scientific journal
• Localization of fractalkine and CX(3)CR1 mRNAs in rat brain: does fractalkine play a role in signaling from neuron to microglia?
  A Nishiyori; M Minami; Y Ohtani; S Takami; J Yamamoto; N Kawaguchi; T Kume; A Akaike; M Satoh
  FEBS LETTERS, 429, 2, 167, 172, Jun. 1998, [Peer-reviewed]
  English, Scientific journal
• Expression of stromal cell-derived factor-1 and CXCR4 chemokine receptor mRNAs in cultured rat glial and neuronal cells
  Y Ohtani; M Minami; N Kawaguchi; A Nishiyori; J Yamamoto; S Takami; M Satoh
  NEUROSCIENCE LETTERS, 249, 2-3, 163, 166, Jun. 1998, [Peer-reviewed]
  English, Scientific journal
• DAMGO recognizes four residues in the third extracellular loop to discriminate between mu- and kappa-opioid receptors
  T Seki; M Minami; T Nakagawa; Y Ienaga; A Morisada; M Satoh
  EUROPEAN JOURNAL OF PHARMACOLOGY, 350, 2-3, 301, 310, Jun. 1998, [Peer-reviewed]
  English, Scientific journal
• beta(2)-Adrenoceptors on the glial cells mediate the induction of interleukin-1 beta mRNA in the rat brain
  E Maruta; K Yabuuchi; A Nishiyori; S Takami; M Minami; M Satoh
  MOLECULAR BRAIN RESEARCH, 49, 1-2, 291, 294, Oct. 1997, [Peer-reviewed]
  English, Scientific journal
• Type 2 interleukin-1 receptor mRNA is induced by kainic acid in the rat brain
  A Nishiyori; M Minami; S Takami; M Satoh
  MOLECULAR BRAIN RESEARCH, 50, 1-2, 237, 245, Oct. 1997, [Peer-reviewed]
  English, Scientific journal
• Intracerebroventricular injection of isoproterenol produces its analgesic effect through interleukin-1 beta production
  K Yabuuchi; E Maruta; J Yamamoto; A Nishiyori; S Takami; M Minami; M Satoh
  EUROPEAN JOURNAL OF PHARMACOLOGY, 334, 2-3, 133, 140, Sep. 1997, [Peer-reviewed]
  English, Scientific journal
• Induction of macrophage inflammatory protein MIP-1 alpha mRNA on glial cells after focal cerebral ischemia in the rat
  S Takami; H Nishikawa; M Minami; A Nishiyori; M Sato; A Akaike; M Satoh
  NEUROSCIENCE LETTERS, 227, 3, 173, 176, May 1997, [Peer-reviewed]
  English, Scientific journal
• Opioids
  M Satoh; M Minami; SC Yoshida; Y Kuraishi
  JAPANESE JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 19, 2, 190, 203, 1997, [Peer-reviewed]
  Japanese, Scientific journal
• Opioid receptors
  M. Minami; S. Kaneko; M. Satoh
  Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme, 42, 3 Suppl, 335, 342, 1997, [Peer-reviewed]
  English
• A single residue, Lys108, of the delta-opioid receptor prevents the mu-opioid-selective ligand [D-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin from binding to the delta-opioid receptor
  M Minami; T Nakagawa; T Seki; T Onogi; Y Aoki; Y Katao; S Katsumata; M Satoh
  MOLECULAR PHARMACOLOGY, 50, 5, 1413, 1422, Nov. 1996, [Peer-reviewed]
  English, Scientific journal
• Localization of mRNA for leukemia inhibitory factor receptor in the adult rat brain
  H Yamakuni; M Minami; M Satoh
  JOURNAL OF NEUROIMMUNOLOGY, 70, 1, 45, 53, Oct. 1996, [Peer-reviewed]
  English, Scientific journal
• Pharmacological characterization of KT-90 using cloned mu-, delta- and kappa-opioid receptors
  S Katsumata; Y Ienaga; M Minami; T Nakagawa; K Kanematsu; M Satoh
  EUROPEAN JOURNAL OF PHARMACOLOGY, 312, 3, 349, 355, Oct. 1996, [Peer-reviewed]
  English, Scientific journal
• Co-localization of mu opioid receptor is greater with dynorphin than enkephalin in rat striatum
  ND Guttenberg; H Klop; M Minami; M Satoh; P Voorn
  NEUROREPORT, 7, 13, 2119, 2124, Sep. 1996, [Peer-reviewed]
  English, Scientific journal
• Biphasic effects of intracerebroventricular interleukin-1 beta on mechanical nociception in the rat
  K Yabuuchi; A Nishiyori; M Minami; M Satoh
  EUROPEAN JOURNAL OF PHARMACOLOGY, 300, 1-2, 59, 65, Apr. 1996, [Peer-reviewed]
  English, Scientific journal
• Induction of interleukin-1 beta mRNA in the hypothalamus following subcutaneous injections of formalin into the rat hind paws
  K Yabuuchi; E Maruta; M Minami; M Satoh
  NEUROSCIENCE LETTERS, 207, 2, 109, 112, Mar. 1996, [Peer-reviewed]
  English, Scientific journal
• Expression of mu- and kappa-, but not delta-, opioid receptor mRNAs is enhanced in the spinal dorsal horn of the arthritic rats
  K Maekawa; M Minami; T Masuda; M Satoh
  PAIN, 64, 2, 365, 371, Feb. 1996, [Peer-reviewed]
  English, Scientific journal
• SUPPRESSION OF NALOXONE-PRECIPITATED WITHDRAWAL JUMPS IN MORPHINE-DEPENDENT MICE BY STIMULATION OF PROSTAGLANDIN EP(3) RECEPTOR
  T NAKAGAWA; M MINAMI; S KATSUMATA; Y IENAGA; M SATOH
  BRITISH JOURNAL OF PHARMACOLOGY, 116, 6, 2661, 2666, Nov. 1995, [Peer-reviewed]
  English, Scientific journal
• Pharmacological study of dihydroetorphine in cloned mu-, delta- and kappa-opioid receptors
  S Katsumata; M Minami; T Nakagawa; T Iwamura; M Satoh
  EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 291, 3, 367, 373, Nov. 1995, [Peer-reviewed]
  English, Scientific journal
• MOLECULAR-BIOLOGY OF THE OPIOID RECEPTORS - STRUCTURES, FUNCTIONS AND DISTRIBUTIONS
  M MINAMI; M SATOH
  NEUROSCIENCE RESEARCH, 23, 2, 121, 145, Sep. 1995, [Peer-reviewed]
  English
• TRANSIENT EXPRESSION OF FGF RECEPTOR-4 MESSENGER-RNA IN THE RAT CEREBELLUM DURING POSTNATAL-DEVELOPMENT
  A MIYAKE; M MINAMI; M SATOH; M OHTA; N ITOH
  MOLECULAR BRAIN RESEARCH, 31, 1-2, 95, 100, Jul. 1995, [Peer-reviewed]
  English, Scientific journal
• DOUBLE IN-SITU HYBRIDIZATION STUDY ON COEXISTENCE OF MU-OPIOID, DELTA-OPIOID AND KAPPA-OPIOID RECEPTOR MESSENGER-RNAS WITH PREPROTACHYKININ-A MESSENGER-RNA IN THE RAT DORSAL-ROOT GANGLIA
  M MINAMI; K MAEKAWA; K YABUUCHI; M SATOH
  MOLECULAR BRAIN RESEARCH, 30, 2, 203, 210, Jun. 1995, [Peer-reviewed]
  English, Scientific journal
• INTRACISTERNAL ADMINISTRATION OF INTERLEUKIN-1-BETA ATTENUATES NALOXONE-PRECIPITATED WITHDRAWAL IN MORPHINE-DEPENDENT
  S KATSUMATA; M MINAMI; T NAKAGAWA; M SATOH
  EUROPEAN JOURNAL OF PHARMACOLOGY, 278, 2, 143, 150, May 1995, [Peer-reviewed]
  English, Scientific journal
• DAMGO, A MU-OPIOID RECEPTOR-SELECTIVE LIGAND, DISTINGUISHES BETWEEN MU-OPIOID AND KAPPA-OPIOID RECEPTORS AT A DIFFERENT REGION FROM THAT FOR THE DISTINCTION BETWEEN MU-OPIOID AND DELTA-OPIOID RECEPTORS
  M MINAMI; T ONOGI; T NAKAGAWA; Y KATAO; Y AOKI; S KATSUMATA; M SATOH
  FEBS LETTERS, 364, 1, 23, 27, May 1995, [Peer-reviewed]
  English, Scientific journal
• EXPRESSION OF INSULIN RECEPTOR-RELATED RECEPTOR MESSENGER-RNA IN THE RAT-BRAIN IS HIGHLY RESTRICTED TO FOREBRAIN CHOLINERGIC NEURONS
  K TSUJIMOTO; N TSUJI; K OZAKI; M MINAMI; M SATOH; N ITOH
  NEUROSCIENCE LETTERS, 188, 2, 105, 108, Mar. 1995, [Peer-reviewed]
  English, Scientific journal
• G(Z) COUPLING TO THE RAT KAPPA-OPIOID RECEPTOR
  HWL LAI; M MINAMI; M SATOH; YH WONG
  FEBS LETTERS, 360, 1, 97, 99, Feb. 1995, [Peer-reviewed]
  English, Scientific journal
• A study on the structural basis of opioid receptors for the subtype-selective binding of damgo, a μ-opioid receptor selective agonist, using chimeric opioid receptors
  Masabumi Minami; Masamichi Satoh
  Folia Pharmacologica Japonica, 106, 162, 166, 1995, [Peer-reviewed]
  English, Scientific journal
• DAMGO, A MU-OPIOID RECEPTOR-SELECTIVE AGONIST, DISTINGUISHES BETWEEN MU-OPIOID AND DELTA-OPIOID RECEPTORS AROUND THEIR FIRST EXTRACELLULAR LOOPS
  T ONOGI; M MINAMI; Y KATAO; T NAKAGAWA; Y AOKI; T TOYA; S KATSUMATA; M SATOH
  FEBS LETTERS, 357, 1, 93, 97, Jan. 1995, [Peer-reviewed]
  English, Scientific journal
• IMMUNOCYTOCHEMICAL LOCALIZATION OF MU-OPIOID RECEPTOR IN THE RAT CAUDATE-PUTAMEN
  T KANEKO; M MINAMI; M SATOH; N MIZUNO
  NEUROSCIENCE LETTERS, 184, 3, 149, 152, Jan. 1995, [Peer-reviewed]
  English, Scientific journal
• Molecular pharmacology of the opioid receptors
  M Satoh; M Minami
  PHARMACOLOGY & THERAPEUTICS, 68, 3, 343, 364, 1995, [Peer-reviewed]
  English
• LOCALIZATION OF TYPE-I INTERLEUKIN-1 RECEPTOR MESSENGER-RNA IN THE RAT-BRAIN
  K YABUUCHI; M MINAMI; S KATSUMATA; M SATOH
  MOLECULAR BRAIN RESEARCH, 27, 1, 27, 36, Nov. 1994, [Peer-reviewed]
  English, Scientific journal
• AN IN-SITU HYBRIDIZATION STUDY ON INTERLEUKIN-1-BETA MESSENGER-RNA INDUCED BY TRANSIENT FOREBRAIN ISCHEMIA IN THE RAT-BRAIN
  K YABUUCHI; M MINAMI; S KATSUMATA; A YAMAZAKI; M SATOH
  MOLECULAR BRAIN RESEARCH, 26, 1-2, 135, 142, Oct. 1994, [Peer-reviewed]
  English, Scientific journal
• INTRATHECAL NEUROMEDIN-C ENHANCES MECHANICAL NOCICEPTION - POSSIBLE INVOLVEMENT OF NMDA RECEPTORS
  T ONOGI; M KAGAWA; M MINAMI; Y KURAISHI; M SATOH
  EUROPEAN JOURNAL OF PHARMACOLOGY, 262, 1-2, 163, 166, Sep. 1994, [Peer-reviewed]
  English
• DIFFERENTIAL EXPRESSION PATTERNS OF MESSENGER-RNAS FOR MEMBERS OF THE FIBROBLAST GROWTH-FACTOR RECEPTOR FAMILY, FGFR-1-FGFR-4, IN RAT-BRAIN
  N YAZAKI; Y HOSOI; K KAWABATA; A MIYAKE; M MINAMI; M SATOH; M OHTA; T KAWASAKI; N ITOH
  JOURNAL OF NEUROSCIENCE RESEARCH, 37, 4, 445, 452, Mar. 1994, [Peer-reviewed]
  English, Scientific journal
• RAT FGF RECEPTOR-4 MESSENGER-RNA IN THE BRAIN IS EXPRESSED PREFERENTIALLY IN THE MEDIAL HABENULAR NUCLEUS
  N ITOH; N YAZAKI; S TAGASHIRA; A MIYAKE; K OZAKI; M MINAMI; M SATOH; M OHTA; T KAWASAKI
  MOLECULAR BRAIN RESEARCH, 21, 3-4, 344, 348, Feb. 1994, [Peer-reviewed]
  English
• IN-SITU HYBRIDIZATION STUDY OF MU-OPIOID AND KAPPA-OPIOID RECEPTOR MESSENGER-RNAS IN THE RAT SPINAL-CORD AND DORSAL-ROOT GANGLIA
  K MAEKAWA; M MINAMI; K YABUUCHI; T TOYA; Y KATAO; Y HOSOI; T ONOGI; M SATOH
  NEUROSCIENCE LETTERS, 168, 1-2, 97, 100, Feb. 1994, [Peer-reviewed]
  English, Scientific journal
• MOLECULAR-CLONING AND IN-SITU HYBRIDIZATION HISTOCHEMISTRY FOR RAT MU-OPIOID RECEPTOR
  M MINAMI; T ONOGI; T TOYA; Y KATAO; Y HOSOI; K MAEKAWA; S KATSUMATA; K YABUUCHI; M SATOH
  NEUROSCIENCE RESEARCH, 18, 4, 315, 322, Jan. 1994, [Peer-reviewed]
  English
• IN-SITU HYBRIDIZATION STUDY OF KAPPA-OPIOID RECEPTOR MESSENGER-RNA IN THE RAT-BRAIN
  M MINAMI; Y HOSOI; T TOYA; Y KATAO; K MAEKAWA; S KATSUMATA; K YABUUCHI; T ONOGI; M SATOH
  NEUROSCIENCE LETTERS, 162, 1-2, 161, 164, Nov. 1993, [Peer-reviewed]
  English, Scientific journal
• IN-SITU HYBRIDIZATION STUDY OF INTERLEUKIN-1-BETA MESSENGER-RNA INDUCED BY KAINIC ACID IN THE RAT-BRAIN
  K YABUUCHI; M MINAMI; S KATSUMATA; M SATOH
  MOLECULAR BRAIN RESEARCH, 20, 1-2, 153, 161, Oct. 1993, [Peer-reviewed]
  English, Scientific journal
• CLONING AND EXPRESSION OF A CDNA FOR THE RAT KAPPA-OPIOID RECEPTOR
  M MINAMI; T TOYA; Y KATAO; K MAEKAWA; S NAKAMURA; T ONOGI; S KANEKO; M SATOH
  FEBS LETTERS, 329, 3, 291, 295, Aug. 1993, [Peer-reviewed]
  English, Scientific journal
• CAPSAICIN-LIKE EFFECT OF (6)-SHOGAOL ON SUBSTANCE P-CONTAINING PRIMARY AFFERENTS OF RATS - A POSSIBLE MECHANISM OF ITS ANALGESIC ACTION
  T ONOGI; M MINAMI; Y KURAISHI; M SATOH
  NEUROPHARMACOLOGY, 31, 11, 1165, 1169, Nov. 1992, [Peer-reviewed]
  English, Scientific journal
• BEHAVIORAL CHARACTERIZATION OF A 5-HT3 RECEPTOR ANTAGONIST, ONDANSETRON, IN RATS
  H TOGASHI; M MATSUMOTO; M YOSHIOKA; M MINAMI; H SAITO
  BIOGENIC AMINES, 9, 1, 15, 27, 1992, [Peer-reviewed]
  English, Scientific journal
• INDUCTION OF INTERLEUKIN-1 BETA MESSENGER-RNA IN RAT-BRAIN AFTER TRANSIENT FOREBRAIN ISCHEMIA
  M MINAMI; Y KURAISHI; K YABUUCHI; A YAMAZAKI; M SATOH
  JOURNAL OF NEUROCHEMISTRY, 58, 1, 390, 392, Jan. 1992, [Peer-reviewed]
  English
• Inhibition of morphine dependence by a lipopolysaccharide from ┣DBPantoea agglomerans(/)-┫DB
  European Cytokine Network, 3, 417, 420, 1992
• INVOLVEMENT OF CENTRAL BETA-ADRENOCEPTORS IN THE INDUCTION OF HYPOTHALAMIC INTERLEUKIN-1-BETA MESSENGER-RNA BY METHAMPHETAMINE
  T YAMAGUCHI; Y KURAISHI; M MINAMI; K YABUUCHI; M SATOH
  NEUROSCIENCE RESEARCH, 12, 3, 432, 439, Nov. 1991, [Peer-reviewed]
  English, Scientific journal
• METHAMPHETAMINE-INDUCED EXPRESSION OF INTERLEUKIN-1-BETA MESSENGER-RNA IN THE RAT HYPOTHALAMUS
  T YAMAGUCHI; Y KURAISHI; M MINAMI; S NAKAI; Y HIRAI; M SATOH
  NEUROSCIENCE LETTERS, 128, 1, 90, 92, Jul. 1991, [Peer-reviewed]
  English, Scientific journal
• EFFECTS OF KAINIC ACID ON MESSENGER-RNA LEVELS OF IL-1-BETA, IL-6, TNF-ALPHA AND LIF IN THE RAT-BRAIN
  M MINAMI; Y KURAISHI; M SATOH
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 176, 2, 593, 598, Apr. 1991, [Peer-reviewed]
  English, Scientific journal
• IMMOBILIZATION STRESS INDUCES INTERLEUKIN-1-BETA MESSENGER-RNA IN THE RAT HYPOTHALAMUS
  M MINAMI; Y KURAISHI; T YAMAGUCHI; S NAKAI; Y HIRAI; M SATOH
  NEUROSCIENCE LETTERS, 123, 2, 254, 256, Feb. 1991, [Peer-reviewed]
  English, Scientific journal
• SEROTONIN, BUT NEITHER NORADRENALINE NOR GABA, INHIBITS CAPSAICIN-EVOKED RELEASE OF IMMUNOREACTIVE SOMATOSTATIN FROM SLICES OF RAT SPINAL-CORD
  Y KURAISHI; M MINAMI; M SATOH
  NEUROSCIENCE RESEARCH, 9, 4, 238, 245, Jan. 1991, [Peer-reviewed]
  English, Scientific journal
• In situ hybridization analysis of the induction of interleukin-1 mRNA by methamphetamine in the rat hypothalamus.
  Molecular and Cellar Neuroscience, 2,259-265, 1991
• CONVULSANTS INDUCE INTERLEUKIN-1-BETA MESSENGER-RNA IN RAT-BRAIN
  M MINAMI; Y KURAISHI; T YAMAGUCHI; S NAKAI; Y HIRAI; M SATOH
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 171, 2, 832, 837, Sep. 1990, [Peer-reviewed]
  English, Scientific journal
• SOMATOSTATIN IS INCREASED IN THE DORSAL-ROOT GANGLIA OF ADJUVANT-INFLAMED RAT
  H OHNO; Y KURAISHI; T NANAYAMA; M MINAMI; M KAWAMURA; M SATOH
  NEUROSCIENCE RESEARCH, 8, 3, 179, 188, Jul. 1990, [Peer-reviewed]
  English, Scientific journal
• ANTINOCICEPTIVE EFFECT OF INTRATHECALLY ADMINISTERED ANTISERUM AGAINST CALCITONIN GENE-RELATED PEPTIDE ON THERMAL AND MECHANICAL NOXIOUS STIMULI IN EXPERIMENTAL HYPERALGESIC RATS
  M KAWAMURA; Y KURAISHI; M MINAMI; M SATOH
  BRAIN RESEARCH, 497, 1, 199, 203, Sep. 1989, [Peer-reviewed]
  English
• ENHANCEMENT OF PREPROTACHYKININ-A GENE-EXPRESSION BY ADJUVANT-INDUCED INFLAMMATION IN THE RAT SPINAL-CORD - POSSIBLE INVOLVEMENT OF SUBSTANCE-P-CONTAINING SPINAL NEURONS IN NOCICEPTION
  M MINAMI; Y KURAISHI; M KAWAMURA; T YAMAGUCHI; Y MASU; S NAKANISHI; M SATOH
  NEUROSCIENCE LETTERS, 98, 1, 105, 110, Mar. 1989, [Peer-reviewed]
  English, Scientific journal
• MODALITY-SPECIFIC ANTINOCICEPTION PRODUCED BY INTRATHECAL INJECTION OF ANTI-SOMATOSTATIN ANTISERUM IN RATS
  H OHNO; Y KURAISHI; M MINAMI; M SATOH
  BRAIN RESEARCH, 474, 1, 197, 200, Nov. 1988, [Peer-reviewed]
  English
• ANTINOCICEPTION INDUCED IN RATS BY INTRATHECAL ADMINISTRATION OF ANTISERUM AGAINST CALCITONIN GENE-RELATED PEPTIDE
  Y KURAISHI; T NANAYAMA; H OHNO; M MINAMI; M SATOH
  NEUROSCIENCE LETTERS, 92, 3, 325, 329, Oct. 1988, [Peer-reviewed]
  English, Scientific journal
• Effect of SM-2470, a newly synthesized α1-adrenoceptor antagonist, on sympathetic nerve activity in anesthetized rats
  M. Yoshioka; M. Matsumoto; H. Togashi; M. Abe; T. Ikeda; K. Morii; M. Minami; H. Saito
  Archives Internationales de Pharmacodynamie et de Therapie, 293, 1, 162, 174, 1988, [Peer-reviewed]
  English, Scientific journal
• Effects of hydralazine on adrenal and cardiac sympathetic nerve activity in anesthetized rats.
  M Yoshioka; H Togashi; M Minami; H Saito
  Research communications in chemical pathology and pharmacology, 54, 3, 313, 20, Dec. 1986, [Peer-reviewed], [International Magazine]
  English, Scientific journal, The present study was carried out to elucidate whether there is a correlation between hydralazine-induced tachycardia and the increase in cardiac sympathetic nerve activity in buffer nerve-intact and debuffered rats. Hydralazine (1 mg/kg, i.v.) produced a significant decrease in mean arterial blood pressure immediately after injection in both buffer nerve-intact rats and debuffered rats. A few min after hydralazine administration, increases in cardiac sympathetic nerve activity and heart rate were observed in both rat groups. Moreover, after hydralazine injection, adrenal sympathetic nerve activity increased in the debuffered rat group. These results suggest that hydralazine-induced tachycardia is not only reflexly induced, but that it is also mediated via direct excitation of the central nervous system in rats.

• Required research activities to overcome addiction problems in Japan
  Kazutaka Ikeda; Soichiro Ide; Hiromi Takahashi-Omoe; Masabumi Minami; Hisatsugu Miyata; Mitsuo Kawato; Hitoshi Okamoto; Tetsuro Kikuchi; Yumiko Saito; Tomoaki Shirao; Yuko Sekino; Toshiya Murai; Toshihiko Matsumoto; Masako Iseki; Yoko Nishitani; Masahiko Sumitani; Hidehiko Takahashi; Shigeto Yamawaki; Tadashi Isa; Yoko Kamio, Taiwanese Journal of Psychiatry, 35, 1, 6, 11, 2021
  Medknow
• 配座制御を鍵とした分子設計によるGABAトランスポーターBGT-1サブタイプ選択的阻害薬の創製研究
  三井桂佑; 末政亮大; 小林嵩明; 人羅菜津子; 藤原広一; 渡邉瑞貴; 南雅文; WELLENDORPH Petrine; 周東智, メディシナルケミストリーシンポジウム講演要旨集, 37th, 2019
• レゾルビンE1の抗うつ作用における内側前頭前野内BDNF,VEGF遊離とmTORC1活性化の役割
  青木駿; 出山諭司; 石村航平; 福田隼; 福田隼; 周東智; 南雅文; 金田勝幸, 次世代を担う創薬・医療薬理シンポジウムプログラム・要旨集, 2019, 2019
• ケタミンの即効性抗うつ作用メカニズムの解明とそれに基づく新規創薬標的の発見
  出山諭司; DUMAN Ronald S.; 南雅文; 金田勝幸, 生体機能と創薬シンポジウム要旨集, 2019, 2019
• コカイン関連記憶の獲得および想起における内側前頭前野グルタミン酸作動性ニューロンの役割
  Zhang Tong; 上居 寛典; 柳田 淳子; 和田 進太郎; 堂本 将輝; 出山 諭司; 宝田 剛志; 檜井 栄一; 崎村 建司; 山中 章弘; 前島 隆司; 三枝 理博; 櫻井 武; 西谷 直也; 永安 一樹; 金子 周司; 南 雅文; 金田 勝幸, 日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集, 28回・48回, 216, 216, Nov. 2018
  日本臨床精神神経薬理学会・日本神経精神薬理学会, Japanese
• レゾルビンE1およびレゾルビンE2の抗うつ作用機序
  鈴木博惠; 出山諭司; 出山諭司; 霜田健斗; 石川由香; 石村航平; 福田隼; 人羅(今村)菜津子; 井手聡一郎; 井手聡一郎; 佐藤公道; 金田勝幸; 周東智; 南雅文, 日本薬学会年会要旨集(CD-ROM), 138th, 2018
• GABAトランスポーターサブタイプ選択的阻害剤の創出を目的とするGABA配座制限誘導体の設計と合成
  末政亮大; 中田和彰; 小林嵩明; 福田隼; 渡邉瑞貴; 井手聡一郎; 人羅菜津子; 南雅文; 周東智, 日本薬学会年会要旨集(CD-ROM), 138th, 2018
• The effects of sexual hormone on the brain area related to parental behavior
  Taiju Amano; Kazuki Ito; Takashi Maejima; Takeshi Sakurai; Masabumi Minami; Kumi Kuroda, JOURNAL OF PHARMACOLOGICAL SCIENCES, 133, 3, S84, S84, Mar. 2017
  English, Summary international conference
• 慢性ストレスと母子分離ストレスの負荷による治療抵抗性うつ病モデル動物作製と側坐核内ドパミン遊離を指標とした脳内報酬系機能評価
  南沙希; 里吉寛; 井手聡一郎; 井手聡一郎; 南雅文, 日本神経精神薬理学会プログラム・抄録集, 47th, 2017
• ヒスタミンH3受容体逆アゴニストは,思い出せなくなった物体記憶を回復させる
  野村洋; 野村洋; 水田弘人; 乗本裕明; 増田文貴; 三浦友樹; 小島寛人; 芦塚あおい; 松河理子; BARAKI Zohal; 人羅(今村)菜津子; 人羅(今村)菜津子; 中山大輔; 石川智愛; 齋藤瞭毅; 佐野大和; 楠原洋之; 南雅文; 高橋英彦; 池谷裕二, 日本神経精神薬理学会プログラム・抄録集, 47th, 2017
• 新規GABAトランスポーター阻害薬候補化合物の薬理活性評価
  佐藤孝行; 井川ありさ; 圓山智嘉史; 末政亮大; 小林嵩明; 有澤光弘; 井手聡一郎; 周東智; 南雅文, 次世代を担う創薬・医療薬理シンポジウムプログラム・要旨集, 2016, 2016
• 三次元多様性を鍵とする分子設計に基づくGABAトランスポーターBGT-1サブタイプ高選択的阻害剤の創製
  末政亮大; 中田和彰; 小林嵩明; 福田隼; 渡邉瑞貴; 柴野さや子; 井川ありさ; 井手聡一郎; 南雅文; 周東智, 次世代を担う有機化学シンポジウム講演要旨集, 14th, 2016
• GABAトランスポーターサブタイプ特異的な新規阻害薬候補化合物の薬理活性評価
  佐藤孝行; 井川ありさ; 圓山智嘉史; 末政亮大; 小林嵩明; 有澤光弘; 井手聡一郎; 周東智; 南雅文, 日本薬学会年会要旨集(CD-ROM), 136th, 2016
• レゾルビンD1,D2の抗うつ作用メカニズムの解明
  石川由香; 出山諭司; 出山諭司; 吉川琴美; 霜田健斗; 人羅(今村)菜津子; 井手聡一郎; 井手聡一郎; 佐藤公道; 南雅文, 日本生物学的精神医学会(Web), 38th, 2016
• ATP受容体P2X7サブタイプ遺伝子多型と疼痛および鎮痛薬感受性との相関
  井手 聡一郎; 西澤 大輔; 福田 謙一; 笠井 慎也; 長谷川 準子; 林田 眞和; 南 雅文; 池田 和隆, 日本生物学的精神医学会・日本神経精神薬理学会合同年会プログラム・抄録集, 37回・45回, 182, 182, Sep. 2015
  日本生物学的精神医学会・日本神経精神薬理学会, Japanese
• CRFによる分界条床核III型神経細胞での抑制性シナプス伝達促進
  長野 雄介; 金田 勝幸; 圓山 智嘉史; 井手 聡一郎; 加藤 総夫; 南 雅文, 日本生物学的精神医学会・日本神経精神薬理学会合同年会プログラム・抄録集, 37回・45回, 173, 173, Sep. 2015
  日本生物学的精神医学会・日本神経精神薬理学会, Japanese
• レゾルビンE2の抗うつ作用に関する検討
  霜田 健斗; 出山 諭司; 井手 聡一郎; 福田 隼; 周東 智; 南 雅文, 日本薬学会年会要旨集, 135年会, 3, 193, 193, Mar. 2015
  (公社)日本薬学会, Japanese
• レゾルビンD1およびD2の抗うつ作用メカニズム
  吉川 琴美; 出山 諭司; 霜田 健斗; 石川 由香; 井手 聡一郎; 南 雅文, 日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集, 24回・44回, 198, 198, Nov. 2014
  日本臨床精神神経薬理学会・日本神経精神薬理学会, Japanese
• リポポリサッカライド誘発うつ病様行動に対するレゾルビンDシリーズの効果
  出山 諭司; 吉川 琴美; 霜田 健斗; 南 雅文, 日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集, 23回・43回, 246, 246, Oct. 2013
  日本臨床精神神経薬理学会・日本神経精神薬理学会, Japanese
• 血液脳関門バリア機能に対するニコチンの作用
  磯 有希奈; 松原 滉; 出山 諭司; 片山 貴博; 南 雅文, 日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集, 23回・43回, 250, 250, Oct. 2013
  日本臨床精神神経薬理学会・日本神経精神薬理学会, Japanese
• Neuronal mechanisms underlying pain-induced negative emotions
  Masabumi Minami, Brain and Nerve, 64, 11, 1241, 1247, Nov. 2012
  Japanese, Book review
• 痛み感受性の遺伝的要因
  井手聡一郎; 南雅文; 池田和隆, ペインクリニック, 33, 1, 67, 74, Jan. 2012
  Japanese
• 痛みによる不快情動生成における分界条床核内CRF神経情報伝達系の役割
  中 誠則; 出山 諭司; 井手 聡一郎; 南 雅文, PAIN RESEARCH, 26, 2, 108, 108, Jul. 2011
  日本疼痛学会, Japanese
• Neuroinflammation and nicotinic acethylcholine receptors in glial cells
  片山 貴博; 南 雅文, 医学のあゆみ, 237, 11, 1065, 1069, 11 Jun. 2011
  医歯薬出版, Japanese
• Neuro-glio-vascular Interaction in Ischemic Brains
  Masabumi Minami, YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 131, 4, 539, 544, Apr. 2011
  Japanese, Book review
• 心と身 : 一個体レベルのシステム科学としての薬理学
  南 雅文, 日本薬理学雑誌, 136, 2, 69, 70, 01 Aug. 2010
  Japanese
• Role of the bed nucleus of the stria terminalis in pain-induced negative emotion
  南 雅文, 医学のあゆみ, 232, 1, 22, 27, 02 Jan. 2010
  医歯薬出版, Japanese
• 培養海馬スライスを用いたミクログリアによる傷害細胞貪食に関する研究
  小林速人; 片山貴博; 岡村敏行; 井手聡一郎; 上原孝; 南雅文, 日本薬理学雑誌, 135, 1, 2010
• Combination of cell culture assays and knockout mouse analyses for the study of opioid partial agonism. (Methods Mol Biol)
  Ide Soichiro; Minami Masabumi; Sora Ichiro; Ikeda Kazutaka, Methods Mol Biol, 617, 363, 374, 2010
• ブトルファノールの鎮痛効果とオピオイド受容体
  井手聡一郎; 南雅文; 池田和隆, 生体の科学, 60, 5, 456, 457, Oct. 2009
  Japanese
• 痛みによる不快情動生成と食欲抑制における分界条床核内ノルアドレナリン神経情報伝達の役割
  仲子 友和; 出山 諭司; 南 雅文, PAIN RESEARCH, 23, 2, 70, 70, Jul. 2008
  日本疼痛学会, Japanese
• 疼痛関連不快情動反応における分界条床核内グルタミン酸神経情報伝達および一酸化窒素の役割
  出山 諭司; 南 雅文, PAIN RESEARCH, 23, 2, 91, 91, Jul. 2008
  日本疼痛学会, Japanese
• 食欲調節における分界条床核内神経情報伝達の役割
  平田 美紀枝; 出山 諭司; 片山 貴博; 南 雅文, 日本薬学会年会要旨集, 128年会, 3, 129, 129, Mar. 2008
  (公社)日本薬学会, Japanese
• Neuronal basis for pain-induced aversion
  Masabumi Minami, Japanese Journal of Neuropsychopharmacology, 28, 1, 37, 41, Feb. 2008
  Japanese, Book review
• 痛みによる不快情動生成の神経機構
  南 雅文, 日本神経精神薬理学雑誌 = Japanese journal of psychopharmacology, 27, 5, 254, 254, 25 Nov. 2007
  Japanese
• 疼痛誘発不快情動反応における分界条床核内コルチコトロピン放出因子(CRF)の関与
  出山 諭司; 南 雅文, PAIN RESEARCH, 22, 2, 64, 64, Jul. 2007
  日本疼痛学会, Japanese
• 疼痛誘発不快情動反応における分界条床核内ノルアドレナリン伝達の関与
  南 雅文; 出山 諭司, PAIN RESEARCH, 22, 2, 64, 64, Jul. 2007
  日本疼痛学会, Japanese
• 痛みによる不快情動生成における分界条床核ノルアドレナリン神経伝達の役割
  出山 諭司; 平田 美紀枝; 中川 貴之; 金子 周司; 南 雅文, 日本薬学会年会要旨集, 127年会, 2, 129, 129, Mar. 2007
  (公社)日本薬学会, Japanese
• 痛みを知る-痛みの中枢回路 痛みと情動-扁桃体およびその関連脳領域の役割
  南雅文, 週刊医学のあゆみ, 223, 9, 700, 705, 2007
• ニューロン傷害によるアストロサイト活性化機構に関する検討
  久米 利明; 神谷 明裕; 片山 貴博; 岡村 敏行; 金子 周司; 赤池 昭紀; 南 雅文, バイオイメージング, 15, 2, 159, 160, 31 Oct. 2006
  Japanese
• Effects of cholesterol biosynthesis-associated compounds on HRD1 expression and protection against hypoxia-induced cell death
  N Takamura; M Kaneko; T Uehara; M Minami; Y Nomura, JOURNAL OF PHARMACOLOGICAL SCIENCES, 100, 290P, 290P, 2006
  English, Summary international conference
• NMDA誘発神経細胞傷害に伴うグリア細胞活性化のメカニズム (生体機能と創薬シンポジウム2005--疾病に関わる生体分子と治療薬) -- (シンポジウム3 虚血性疾患と難治性神経変性疾患の病態と治療)
  南 雅文; 片山 貴将; 佐藤 公道, 薬学雑誌, 125, 57, 60, 08 Sep. 2005
  日本薬学会, Japanese
• 嫌悪系--苦痛の制御メカニズム (特集・情動--喜びと恐れの脳の仕組み)
  南 雅文, 生体の科学, 56, 1, 26, 31, Jan. 2005
  金原一郎記念医学医療振興財団, Japanese
• Distinct mechanisms underlying pleasure and analgesia
  IDE Soichiro; MINAMI Masabumi; SATOH Masamichi; SORA Ichiro; IKEDA Kazutaka, Folia Pharmacologica Japonica, 125, 1, 11, 15, 01 Jan. 2005
  近年，疼痛緩和ケアが重視される中で，情動が病態や治療に与える影響が注目されている．オピオイド神経系は，情動の中でも快と痛みに深く関係しており，その作動薬であるモルヒネなど麻薬性鎮痛薬は有用な鎮痛効果をもたらす．また，痛みを感じている状況下では依存が形成されないことなどから，オピオイドの快と鎮痛作用が分離出来る可能性が示唆されている．近年，ノックアウトマウスを用いた実験などでは，麻薬性鎮痛薬の主たる作用部位であるµオピオイド受容体が，モルヒネを始めとした多くの麻薬性鎮痛薬の鎮痛効果，報酬効果において中心的な役割を果たすことが示されてきた．しかし，オピオイド鎮痛薬の一つであるブプレノルフィンでは，µオピオイド受容体が欠損すると，鎮痛効果は完全に消失するが，報酬効果は残存することが明らかになった．オピオイドによる快と鎮痛発生機構はやはり一部異なると考えられる．また，アルコールや覚醒剤の報酬効果と鎮痛効果においてもメカニズムの違いが明らかになりつつある．快と痛みの詳細なメカニズムの解明は，Quality of Life（QOL）の向上をもたらすと考えられ，今後さらなる研究が期待される．, The Japanese Pharmacological Society, Japanese
• Roles of the amygdala in pain-related aversive responses
  MINAMI Masabumi; SATOH Masamichi, Folia Pharmacologica Japonica, 125, 5-9, 1, 5, 9, 2005
  「痛み」は感覚的成分（sensory component）と感情的あるいは情動的成分（affectiveあるいはemotional component）からなる．これまでに感覚的成分に関しては精力的に研究されその分子機構も次第に明らかになりつつあるが，感情的成分に関する研究は未だ緒についたばかりである．本稿では，「痛み」の感情的成分である「負の情動反応」における扁桃体の役割とそれに関連する神経情報伝達機構について筆者らの研究成果を紹介する．ホルマリン後肢皮下投与により惹起される体性痛（somatic pain）により扁桃体基底外側核においてc-fos mRNA発現が誘導されたが，扁桃体中心核では発現誘導されなかった．一方，酢酸腹腔内投与による内臓痛（visceral pain）ではc-fos mRNA発現は中心核で誘導されるが，基底外側核では誘導されなかった．また，ホルマリンにより惹起される場所嫌悪反応は，基底外側核あるいは中心核のいずれかを予め破壊することで著しく抑制されたが，酢酸による場所嫌悪反応は，中心核の破壊によってのみ抑制され基底外側核の破壊では影響を受けなかった．これらの結果は，「痛み」の感情的成分である「負の情動反応」に関わる神経回路が，体性痛と内臓痛とでは異なることを示唆している．ホルマリンによる体性痛の際には基底外側核においてグルタミン酸遊離が増加し，NMDA受容体拮抗薬の基底外側核への局所投与によりホルマリンによる場所嫌悪反応が抑制された．さらに，基底外側核へのモルヒネ局所投与はホルマリンによるグルタミン酸遊離と場所嫌悪反応をともに抑制した．これらの知見は，ホルマリン投与により引き起こされる「負の情動反応」に基底外側核でのNMDA受容体を介した神経情報伝達が重要な役割を果たしていることを示唆している．また，モルヒネがこの情報伝達を抑制的に調節することも明らかとなり，モルヒネの鎮痛作用には，「痛み」の感覚的成分である痛覚情報伝達を抑制するという直接的な作用機序だけでなく，「痛み」の感情的成分である「負の情動反応」を抑制するという作用機序も関与していることが考えられる．
  , The Japanese Pharmacological Society, Japanese
• Neuro-glio-vascular interaction
  MINAMI Masabumi, 日本薬理学雑誌 : FOLIA PHARMACOLOGICA JAPONICA, 124, 2, 126, 126, 01 Aug. 2004
  Japanese
• 新規オピオイドμ受容体選択的リガンドK-8のマウスにおける鎮痛作用
  小松紘子; 井手総一郎; 南雅文; 岩村樹憲; 佐藤公道, 日本薬理学雑誌, 123, 2, 2004
• 海馬におけるサイトカインの発現
  生体の科学, 55, 585-589, 2004
• 脳とケモカイン
  脳２１, 6, 103-107, 2003
• オピオイド受容体と鎮痛機構
  CLINICAL NEUROSCIENCE, 20, 1106, 1108, 2002
• 虚血性脳細胞障害におけるケモカインの役割
  南 雅文; 高見 新也; 永田 泉; 名村 尚武; 佐藤 公道, 日本神経精神薬理学雑誌 = Japanese journal of psychopharmacology, 21, 6, 221, 221, 25 Dec. 2001
  Japanese
• モルヒネ依存ラットのナロキソン誘発場所嫌悪反応における扁桃体中心核の関与
  渡辺 豪; 中川 貴之; 山本 梨恵; 前田 哲史; 南 雅文; 佐藤 公道, 日本神経精神薬理学雑誌 = Japanese journal of psychopharmacology, 21, 6, 351, 351, 25 Dec. 2001
  Japanese
• Cytokines and chemokines: Mediators for intercellular communication in the brain
  M. Minami, Yakugaku Zasshi, 121, 12, 875, 885, 2001
  Japanese, Book review
• Antinociceptive effects of intracerebroventricularly administered ATP receptor agonists in the rats
  FUKUI Masato; NAKAGAWA Takayuki; MINAMI Masabumi; SATOH Masamichi, Pain research : the journal of the Japanese Society for the Study of Pain = 日本疼痛学会誌, 15, 3, 151, 151, 02 Dec. 2000
  Japanese
• Chemokines as mediators for intercellular communication in the brain
  Masabumi Minami; Masamichi Satoh, Folia Pharmacologica Japonica, 115, 4, 193, 200, 2000
  Japanese, Book review
• Chemokines as mediators for intercellular communication in the brain
  MINAMI Masabumi; SATOH Masamichi, Folia Pharmacologica Japonica, 115, 4, 193, 200, 2000
  Chemokines constitute a large and still growing family of structurally-related small (8-10 kDa) cytokines that have chemotactic activity for leukocytes. Recently, some receptors for chemokines were reported to be used as a co-receptor by HIV at infection. In addition to their well-established role in inflammatory response and recently-reported role as a co-receptor for HIV, recent data suggest that chemokines and their receptors physiologically and pathologically play crucial roles as the mediators for intercellular communication among the cells intrinsic to and recruited into the brain; i.e., neurons, astrocytes, microglia, endotherial cells and leukocytes. Some chemokines such as SDF-1 and fractalkine are constitutively produced in the brain, implicating that they have an important role in maintenance of CNS homeostasis or determination of the patterning of neurons and or glial cells in developing brain and normal adult brain. Chemokines such as MCP-1, MIP-1α and CINC were shown to be induced by various neuroinflammatory stimuli, suggesting that they are involved in various neurodegenerative diseases such as multiple sclerosis, Alzheimer's disease, stroke and AIDS dementia syndrome. Chemokines and their receptors are potential targets for therapeutic intervention in neurodegenerative diseases., The Japanese Pharmacological Society, Japanese
• オピオイド受容体
  蛋白質核酸酵素（増刊号「創薬−戦略的アプローチから先端的医療まで」）, 45, 985(233)-990(238), 2000
• Expression of calcitonin receptor mRNA in mouse brain serotonergic neurons
  MINAMI Masabumi; NAKAMOTO Hiromitsu; SOEDA Yuko; TAKAMI Shinya; SATOH Masamichi, Pain research : the journal of the Japanese Society for the Study of Pain = 日本疼痛学会誌, 14, 3, 8, 8, 11 Dec. 1999
  Japanese
• オピオイド受容体
  生体の科学（神経系に作用する薬物マニュアル1998）, 49, 392, 395, 1998
• 脳虚血によるサイトカインの誘導とニューロン死
  医学のあゆみ, 186, 801, 802, 1998
• 変異型ノシセプチン受容体を用いたリガンド認識機構の解析
  佐藤公道, 医学のあゆみ, 185, 11, 783, 787, 1998
  医歯薬出版
• A possible mechanism of inhibition of naloxone-evoked withdrawal syndrome through EP3 receptor in morphine-dependent rats
  SATOH Masamichi; MINAMI Masabumi; MASUDA Takahiro; NAKAGAWA Takahiro, 日本神経精神薬理学雑誌 = Japanese journal of psychopharmacology, 17, 6, 250, 250, 25 Dec. 1997
  Japanese
• オピオイド受容体「受容体1997」
  生体の科学, 48, 5, 393, 396, 1997
• オピオイド類「ニューロトランスミッター・トウディ」
  神経精神薬理, 19, 190, 203, 1997
• オピオイド受容体「脳における情報伝達-神経機能素子と素過程」
  蛋白質核酸酵素, 42, 3, 335, 342, 1997
• An accelerated stroke model induced by chronic inhibition of the L-arginine/nitric oxide pathway
  H. Togashi; M. Yoshioka; I. Sakuma; M. Matsumoto; M. Minami; H. Saito, Japanese Heart Journal, 36, 4, 530, 1995, [Peer-reviewed]
  International Heart Journal Association, English
• オピオイド受容体の構造、機能、分布
  南 雅文; 佐藤 公道, 生化学, 66, 8, 1134, 1138, 1994
  日本生化学会, Japanese
• Low cerebral vitamin B12 levels in SHR
  M. Minami; K. Ueno; T. Endo; H. Togashi; M. Yoshioka; H. Saito, Japanese Heart Journal, 32, 4, 578, 1991, [Peer-reviewed]
  English
• Neurochemical study on stroke-prone SHR using determination of acetylcholine level in the cerebrospinal fluid
  H. Togashi; M. Matsumoto; M. Yoshioka; K. Morii; M. Hirokami; M. Minami; H. Saito, Japanese Heart Journal, 32, 4, 573, 1991, [Peer-reviewed]
  English
• Sensitive method for determination of monoamine and acetylcholine concentration in cerebrospinal fluid in normotensive and spontaneously hypertensive rats
  H. Togashi; M. Matsumoto; M. Yoshioka; M. Minami; H. Saito, Japanese Heart Journal, 31, 4, 548, 1990, [Peer-reviewed]
  English

• 扁桃体基底外側核へのモルヒネ微量注入による疼痛関連情動反応の抑制
  「痛み臨床における鎮痛薬・オピオイドの選択」（鎮痛薬・オピオイドペプチド研究会 編）メディカル・パブリケーションズ, 2003
• ケモカイン受容体と虚血性脳細胞障害
  別冊・医学のあゆみ「７回膜貫通型受容体研究の新展開−ポストゲノム時代の受容体研究のゆくえ」, 2001
• ヒト型オピオイド受容体を用いた拮抗性鎮痛薬の薬効評価
  別冊・医学のあゆみ「７回膜貫通型受容体研究の新展開−ポストゲノム時代の受容体研究のゆくえ」, 2001
• ノシセプチン受容体リガンド結合の分子薬理学的検討
  「オピオイドの基礎と臨床」, 2000
• クローン化オピオイド受容体を用いた拮抗性鎮痛薬の薬理学的性質の解析
  「疼痛治療の現状と展望-臨床および基礎の立場から-」, 1998
• オピオイド受容体の構造-受容体構造とリガンド選択性-
  オピオイド-適正使用と最近の進歩-, 1997
• オピオイド
  最新 脳と神経科学シリーズ４，最新の伝達物質−受容体の分子機構と関連神経疾患（メディカルビュー社）, 1996

• 卒業研究準備実習Ⅰ, 2024年, 学士課程, 薬学部
• 大学院共通授業科目（教育プログラム）：脳科学研究の展開, 2024年, 修士課程, 大学院共通科目
• 卒業研究準備実習Ⅱ, 2024年, 学士課程, 薬学部
• 生命医薬科学概論, 2024年, 修士課程, 生命科学院
• 薬学論文講読演習Ⅰ, 2024年, 学士課程, 薬学部
• 大学院共通授業科目（教育プログラム）：脳科学入門, 2024年, 修士課程, 大学院共通科目
• 薬学論文講読演習Ⅱ, 2024年, 学士課程, 薬学部
• 医療薬学特論, 2024年, 修士課程, 生命科学院
• 薬学論文講読演習Ⅲ, 2024年, 学士課程, 薬学部
• 大学院共通授業科目（教育プログラム）：脳科学研究の展開, 2024年, 修士課程, 大学院共通科目
• 薬学総合演習, 2024年, 学士課程, 薬学部
• 薬理学Ⅳ, 2024年, 学士課程, 薬学部
• 薬学卒業研究, 2024年, 学士課程, 薬学部
• 薬理学Ⅲ, 2024年, 学士課程, 薬学部
• 薬科学演習, 2024年, 学士課程, 薬学部
• 薬理学Ⅰ, 2024年, 学士課程, 薬学部
• 薬科学論文講読演習, 2024年, 学士課程, 薬学部
• 薬理学Ⅱ, 2024年, 学士課程, 薬学部
• 薬科学卒業研究, 2024年, 学士課程, 薬学部
• 生命科学研究, 2024年, 修士課程, 生命科学院
• 生命科学実習, 2024年, 修士課程, 生命科学院
• 生命科学論文講読Ⅰ, 2024年, 修士課程, 生命科学院
• 生命科学論文講読Ⅱ, 2024年, 修士課程, 生命科学院
• 生命科学特別研究, 2024年, 博士後期課程, 生命科学院
• 生命科学文献講読, 2024年, 博士後期課程, 生命科学院
• 臨床薬学特別研究, 2024年, 博士後期課程, 生命科学院
• 臨床薬学論文講読Ⅰ, 2024年, 博士後期課程, 生命科学院
• 臨床薬学論文講読Ⅱ, 2024年, 博士後期課程, 生命科学院
• 臨床薬学論文執筆演習, 2024年, 博士後期課程, 生命科学院

• 疼痛学会
• 北米神経科学学会(Society for Neuroscience)
• 薬学会
• 神経化学会
• 神経科学学会
• 薬理学会
• Society for Neuroscience
• The Japanese Association for the Study of Pain
• The Japanese Society for Neurochemistry
• The Japan Neuroscience Society
• The Pharmaceutical Society of Japan
• The Japanese Pharmacological Society

• 慢性痛・慢性ストレスによる抑うつ・不安情動生成を制御するレジリエンス機構の解明
  科学研究費助成事業
  01 Apr. 2023 - 31 Mar. 2026
  南 雅文
  ヒトを含む哺乳類には、慢性痛・慢性ストレスによる抑うつ・不安情動を制御し、うつ病や不安障害の発症を防ぐ脳内レジリエンス機構が備わっていると考えられる。本研究は、申請者のこれまでの研究により、慢性痛・慢性ストレス時の抑うつ・不安情動生成への関与が示された分界条床核内の神経可塑的変化に焦点を当て、この神経可塑的変化を抑制・回復させる神経機構を明らかにすることにより、脳内レジリエンス機構を解明することを目的とする。受容体作動薬・拮抗薬を用いた従来の薬理学的・電気生理学的解析に加え、光遺伝学・化学遺伝学を用いた神経機能解析や蛍光イメージングによるインビボ神経活動計測などの先端的解析手法を融合的に用いて、慢性痛・慢性ストレスによる抑うつ・不安情動生成を制御するレジリエンス機構とその破綻メカニズムを明らかにすることにより、うつ病や不安障害の神経機構の理解や治療標的の同定につながる独創的な研究成果を得ることを目指す。これまでの研究により、腹側被蓋野や視床下部外側野に出力する分界条床核神経が慢性痛時に抑制されることが抑うつ・不安情動亢進に関与することが示されている。そこで2023年度は、分界条床核出力神経に興奮性入力を送っている神経回路を同定するため、候補となる脳部位にチャネルロドプシン２を発現するウイルスを注入した後、分界条床核を含む脳スライスを作製し、脳スライスに光照射した際の分界条床核出力神経への入力をパッチクランプ法による電気生理学的手法を用いて検討し、脳内レジリエンス機構に関与する可能性のある神経路の同定を行った。
  日本学術振興会, 基盤研究(B), 北海道大学, 23K27329
• ＡＩによる行動解析と神経活動イメージングを駆使した新しい行動薬理学の創成
  科学研究費助成事業
  09 Jul. 2021 - 31 Mar. 2024
  南 雅文
  本研究では、ディープラーニングなどのＡＩ技術を駆使した最先端の画像解析により自由行動下の病態モデル動物から仮説フリーに行動情報の収集・解析を行うことで、これまで研究者が気づき得なかった評価項目を抽出しうる新しい行動薬理試験を構築する。さらに、近年進歩が著しい、カルシウムイメージングを用いたインビボ神経活動計測と組み合わせることにより、行動情報と脳内神経活動の相関を明らかにすることで、精神変容・疼痛や薬物作用を鋭敏かつ詳細に解析できる新しい行動薬理学を創成する。2021年度は、ニコチン依存の神経機構解析のため、ニコチン退薬による嫌悪行動を、条件付け場所嫌悪性試験を用いて解析し、分界条床核におけるノルアドレナリン神経情報伝達の関与を明らかにした。さらに、世界保健機関（WHO）の国際疾病分類第11回改訂版（ICD-11）に、ゲーム障害(gaming disorder)の定義が収載されるなど、ゲームやWEBに対する行動嗜癖が今後益々問題になっていくことが考えられるため、行動嗜癖の神経機構解析や治療薬・治療法開発に役立つ新しい行動試験系を開発することを目指し、マウスが好んで行う輪回し行動に対する行動嗜癖の形成と、報酬行動や依存に重要な役割を果たす側坐核内ドパミン遊離との関連を検討するための実験系を構築した。2022年度は、輪回し行動に対する行動嗜癖形成後のマウスの行動を、例えば、輪回し装置を撤去した場合などの、様々なシチュエーション下で記録し、ＡＩ技術を駆使した画像解析により行動嗜癖を形成していないマウスとの行動の違いを明らかにすることで、行動嗜癖を評価するための行動試験系を確立する。また、ドパミンをはじめとする脳内神経伝達物質の遊離変化との相関を解析し、行動嗜癖の神経機構解明のための手がかりを得る。
  日本学術振興会, 挑戦的研究(萌芽), 北海道大学, 21K19318
• 分界条床核での神経情報伝達可塑的変化に着目した抑うつ・不安情動生成の分子機構解明
  科学研究費助成事業
  01 Apr. 2020 - 31 Mar. 2023
  南 雅文
  慢性痛とうつ病・不安障害の併発率が高いことから両者に共通の神経基盤の存在が推測される。申請者らはこれまで、痛みによる負情動生成に分界条床核における神経情報伝達が関与していることを明らかにしてきた。そこで本研究では、分界条床核での神経情報伝達可塑的変化に焦点を当てた研究により、慢性痛による抑うつ・不安惹起の脳内メカニズムを明らかにすることを目的とする。2020年度は、慢性痛時に分界条床核から外側視床下部に投射する神経路が抑制されることにより不安様行動が亢進することを明らかにした。2021年度は、分界条床核から外側視床下部に投射する神経を制御する上流の神経細胞の同定を行った。分界条床核においてCARTペプチドを産生する神経細胞（以下、CART神経）特異的にCreリコンビナーゼを発現する遺伝子組み換えマウスを用いてCART神経に光感受性イオンチャネルを発現させた。当該マウスより作製した脳スライスを用いた電気生理学的解析により、CART神経の活性化が分界条床核から外側視床下部に投射する神経細胞への抑制性入力を増加させることを明らかにした。さらに、改変型GPCR(hM4Di)とその特異的リガンドであるClozapine-N-oxide（CNO）を用いたDREADD法によりCART神経を抑制すると、慢性痛により増加した分界条床核から外側視床下部に投射する神経細胞への抑制性入力が減少するとともに、慢性痛により亢進した不安様行動が抑制されることを明らかにした。以上より、慢性痛時には、分界条床核内CART神経の活動が亢進し、分界条床核から外側視床下部に投射する神経路が抑制されることにより不安様行動が亢進していることが考えられた。
  日本学術振興会, 基盤研究(B), 北海道大学, 20H03389
• ストレス関連疾患を担う機能性脂質の探索と機能解析に基づく臨床応用のための技術基盤の創出
  革新的先端研究開発支援事業
  Oct. 2017 - Mar. 2023
  古屋敷 智之
  国立研究開発法人日本医療研究開発機構, Competitive research funding
• International research development of thermal biology
  Grants-in-Aid for Scientific Research
  06 Nov. 2015 - 31 Mar. 2021
  Tominaga Makoto
  Members of Grant-in-Aid for Scientific Research on Innovative Areas ‘Thermal Biology’ lead the researches regarding temperature sensation and temperature response systems including development of temperature detection and control devices with high resolution and accuracy within the cells and organs. They performed international collaboration researches about thermal biology with 48 institutes in 20 countries, and made 136 presentations and published 47 international papers. In addition, Thermal Biology Training Course was organized in Okazaki in April, 2019. Our research teams could lead the international thermal biology researches with superiority by these coordinated international collaborations.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), 15K21744
• 神経路特異的薬理学とインビボ神経活動イメージングを駆使した脳身連関の神経機構解明
  科学研究費助成事業（挑戦的研究（萌芽））
  Apr. 2019 - Mar. 2021
  南 雅文
  文部科学省, Principal investigator, Competitive research funding
• 慢性痛による抑うつ・不安の惹起に関わる負情動神経回路の可塑的変化の神経機構解明
  科学研究費助成事業（基盤研究（Ｂ））
  Apr. 2017 - Mar. 2020
  南 雅文
  文部科学省, Principal investigator, Competitive research funding
• 温度による行動制御の基盤となる快・不快情動生成機構の解明
  科学研究費助成事業（新学術領域研究（研究領域提案型））
  Jul. 2015 - Mar. 2020
  南 雅文
  文部科学省, Principal investigator, Competitive research funding
• 脳腸連関の統合的理解に基づく新しい創薬標的探索を指向した萌芽的研究
  科学研究費助成事業（挑戦的研究（萌芽））
  Apr. 2017 - Mar. 2019
  南 雅文
  文部科学省, Principal investigator, Competitive research funding
• Elucidation of neural GABA transporter function by developing novel subtype-selective inhibitors
  Grants-in-Aid for Scientific Research
  2015 - 2016
  MINAMI Masabumi; SHUTO Satoshi
  Compound B, a candidate of the selective inhibitor for the BGT-1 subtype of the GABA transporters, showed an antidepressant effect in the tail suspension test. This compound showed high binding affinity and agonistic activity on GABAA receptors. It did not bind to GABAB receptors. These results suggested that the antidepressant effect of the compound B is due to the inhibition of BGT-1 or the combined action of BGT-1 inhibition and GABAA receptor activation. In order to obtain a compound which does not act on GABA receptors but inhibits BGT-1 selectively, four compounds were newly synthesized. However, none of them showed BGT-1 inhibitory effect.
  Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, Principal investigator, Competitive research funding, 15K14960
• 慢性ストレス・慢性疼痛による分界条床核－腹側被蓋野神経回路の機能的変化
  科学研究費補助金(新学術領域研究(研究領域提案型))
  2015 - 2016
  南 雅文
  我々は痛みによる不快情動生成時に背外側分界条床核（dlBNST）において放出されるコルチコトロピン放出因子（CRF）について、電気生理学手法を用いてその生理的・病態生理的機能を調べてきた。dlBNST神経細胞は殆どがGABA作動性であるが電流注入に対する応答様式からⅠ、Ⅱ、Ⅲ型に分類される。これまでにCRFがⅡ型細胞に対し脱分極を誘導することを明らかにしてきた。本研究ではまず慢性疼痛モデルラットおよび対照群ラットからdlBNSTを含む脳スライスを作製し、ホールセルパッチクランプ記録を行った。電気刺激誘発性興奮性シナプス後電流(eEPSC)に対するCRFの効果を調べた。対照群ではⅡ型細胞でeEPSCの振幅が増大したが、慢性疼痛群では変化が認められなかった。逆にCRF1受容体阻害薬NBI27914処置によって慢性疼痛群のeEPSCの振幅は減少したが、対照群では変化しなかった。慢性疼痛時には内因性CRF遊離が亢進しdlBNSTのⅡ型細胞でのeEPSCを持続的に増強している可能性が考えられた。次に、dlBNST内ローカルネットワークに対するCRFの効果について調べた。Ⅲ型細胞から自発的抑制性シナプス後電流(sIPSC)を記録し、CRFを作用させるとsIPSCの発生頻度が上昇した。この現象はテトロドトキシン存在下では観察されなかった。CRFによって脱分極するⅡ型細胞が介在細胞として働くことで、Ⅲ型細胞の活動を抑制的に調節する可能性が考えられた。不快情動生成時にはⅡ型細胞がCRFに応答して活性化することでⅢ型細胞に対する抑制入力を増大させ、他の神経核への出力を抑制することが示唆された。
  文部科学省, 新学術領域研究(研究領域提案型), 北海道大学, Principal investigator, Competitive research funding, 15H01273
• Elucidation of neural mechanisms for negative emotion and its alteration under the pathological conditions: Study with focusing on the bed nucleus of the stria terminalis
  Grants-in-Aid for Scientific Research
  2014 - 2016
  MINAMI Masabumi; KANEDA Katsuyuki; IDE Soichiro; YAMANAKA Akihiro
  Mammals including humans are thought to have acquired and evolved neuronal mechanisms for negative emotion, such as depression and anxiety, as a biological defense system that protects themselves by suppressing their activities and raising vigilance against the surroundings, when they are in dangerous condition. Therefore, in order to understand the neuronal mechanisms of depressive disorders and anxiety disorders, it is necessary to clarify the neuronal mechanisms for negative emotion from the viewpoint as a biological defense system and to analyze the changes of such mechanisms in patients and disease model animals. We have been studying with focusing on the bed nucleus of the stria terminalis (BNST), and demonstrated that activation of BNST neurons by CRF suppresses the dopaminergic neurons in the ventral tegmental area (VTA) to produce pain-induced negative emotion, and that neuroplastic alteration in the BNST induces sustained suppression of VTA dopaminergic neurons.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Principal investigator, Competitive research funding, 26290020
• Medicinal chemical study by the three-dimensional structural diversity-oriented strategy based on the characteristic steric and stereoelectronic features of cyclopropane
  Grants-in-Aid for Scientific Research
  01 Apr. 2012 - 31 Mar. 2015
  SHUTO Satoshi; FUKUDA Hayato; MINAMI Masabumi; HIGASHIDA Haruhiro; HIROKAWA Takatugu
  Cyclopropane is very effective for conformational restriction of compounds due to the characteristic steric and stereoelectronic features, which are sic/trans-restriction, cyclopropylic strain, and bisected conformational preference. We devised the three-dimensional structural diversity-oriented conformational restriction strategy based on the characteristic features of cyclopropane, by which a variety of conformationally restricted analogs of conformationally flexible biologically active prototype compounds were designed and synthesized. Thus, we successfully identified highly potent compounds, which are a GABA transporter subtype BGT-1 inhibitor, proteasome inhibitors, and β-secretase (BASE) inhibitors.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 24390023
• うつ病・不安障害モデル動物における分界条床核神経回路の機能的変化
  科学研究費補助金(新学術領域研究(研究領域提案型))
  2013 - 2014
  南 雅文
  我々はこれまでに、分界条床核２型神経細胞の活性化が嫌悪情動を惹起することを報告している。分界条床核２型神経細胞はコルチコトロピン放出因子（CRF）の刺激により活性化することも明らかにしているが、本年度の研究ではCRFによる２型神経細胞活性化が、アデニル酸シクラーゼーcAMPーPKA系の活性化によることを示し、嫌悪情動を惹起する２型神経細胞内の情報伝達機構を明らかにした。また、我々は、これまでに、分界条床核から腹側被蓋野に投射する神経が腹側被蓋野ドパミン神経の活動を調節する可能性を報告していることから、慢性疼痛や慢性ストレスが腹側被蓋野ドパミン神経活動に及ぼす影響を検討したところ、本来、報酬提示時に観察される腹側被蓋野ドパミン神経活動の亢進が、慢性疼痛モデル動物や慢性ストレス負荷動物では観察されないことが明らかとなった。ドパミン神経活動を調節する神経機構の変化、すなわち、分界条床核から腹側被蓋野にかけての神経回路あるいはその周辺の神経回路の変化が、うつ病のマイクロエンドフェノタイプとなる可能性が考えられる。この仮説を検証するためには慢性疼痛モデル動物や慢性ストレス負荷動物などの成獣のラット・マウス脳より作製した脳スライスを用いた電気生理学的手法による神経回路の詳細な解析が必要である。そのため、今年度は、成獣ラット脳由来スライスを用いた脳スライスパッチクランプによる電気生理学的解析手法の導入も行った。
  文部科学省, 新学術領域研究(研究領域提案型), 北海道大学, Principal investigator, Competitive research funding, 25116501
• Study on the molecular mechanisms for interaction between mesenchymal stem cells and blood brain barrier using real-time imaging
  Grants-in-Aid for Scientific Research
  2013 - 2014
  MINAMI Masabumi; ISO Yukina; MATSUBARA Akira; MINAMISHIMA Takuya
  We carried out antibody array analysis to identify the proteins contained in mouse astrocyte-conditioned medium (ACM), and examined the effects of those proteins on the blood-brain barrier (BBB) function using a mouse in vitro BBB model. We found that leukemia inhibitory facto (LIF) was contained in ACM and significantly attenuated barrier function. Because LIF belongs to Interleukin (IL)-6 family, we examined the effect of other family members IL-6 and oncostatin M on BBB function. Oncostatin M, but not IL-6, significantly attenuated barrier function. Further study for the molecular mechanism of the effects of LIF and oncostatin M may lead to development of the method to control BBB function.
  Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, Principal investigator, Competitive research funding, 25670033
• Pathophysiological analysis for the ischemic brain damage using in vitro blood-brain barrier system
  Grants-in-Aid for Scientific Research
  2011 - 2012
  SHIMOHAMA Shun; MINAMI Masabumi
  To study transmigration of mesenchymal stem cells (MSCs) across the blood-brain barrier (BBB), we developed an in vitro BBB system consisting of rat brain microvascular endothelial cells (BMECs). Time-lapse imaging using this system revealed that MSCs transmigrated across the BMEC monolayer through transiently formed intercellular gaps between the BMECs. In addition, we developed an in vitro imaging system for simultaneous analysis in real time between claudin-5, a tight junction protein, and intracellular calcium dynamics in BMECs during MSC transmigration.
  Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Sapporo Medical University, 23659460
• Study on neuronal mechanisms for negative emotion using behavioral and optogenetical analyses
  Grants-in-Aid for Scientific Research
  2011 - 2012
  MINAMI Masabumi; KANEDA Katsuyuki; IDE Soichiro
  Behavioral studies revealed the opposing roles of corticotropin-releasing factor (CRF) and neuropeptide Y (NPY) within the bed nucleus of the stria terminalis (BNST) in the negative affective component of pain in rats. Electrophysiological studies demonstrated that CRF and NPY selectively act on BNST type II neurons, and activates and suppresses these neurons, respectively. Histochemical analyses showed that most of BNST output neurons projecting to the VTA are GABAergic neurons, which synapse onto VTA GABAergic neurons, suggesting the excitatory drive from the BNST to the VTA dopaminergic neurons via a disinhibition mechanism. Pain-induced release of CRF within the BNST may activate BNST type II neurons, which could suppress VTA-projecting BNST output neurons, thereby attenuating the excitatory drive to the VTA dopaminergic neurons. Pain-induced negative emotion may be due to the suppression of VTA dopaminergic neurons via the processing of pain information in the BNST.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Principal investigator, Competitive research funding, 23300130
• Exploratory research for the mechanisms underlying protective effects of bone marrow mesenchymal stem cells against brain damages
  Grants-in-Aid for Scientific Research
  2011 - 2011
  MINAMI Masabumi; KATAYAMA Takahiro
  To study transmigration of mesenchymal stem cells (MSCs) across the blood-brain barrier (BBB), we developed an in vitro BBB system consisting of rat brain microvascular endothelial cells (BMECs). Time-lapse imaging using this system revealed that MSCs transmigrated across the BMEC monolayer through transiently formed intercellular gaps between the BMECs. In addition, we developed an in vitro imaging system for simultaneous analysis in real time between claudin-5, a tight junction protein, and intracellular calcium dynamics in BMECs during MSC transmigration.
  Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, Principal investigator, Competitive research funding, 23659028
• インビトロ血液脳関門システムによる分子・細胞動態リアルタイムイメージング法の開発
  科学研究費補助金(挑戦的萌芽研究)
  2009 - 2010
  南 雅文
  骨髄間葉系幹細胞(MSC)の静脈内投与は、脳梗塞後の神経機能障害を改善する。昨年度は、マクロファージやミクログリアの脳微小血管内皮細胞(BMEC)層の通過機構に関して検討を行ってきたが、今年度は、臨床応用が期待されているMSCの血液脳関門(BBB)通過機構の解析を行った。はじめに、MSCのBBB通過機構の解析に用いるインビトロ評価系を、BMECからなるインビトロBBBモデルとMSCを組み合わせることで構築した。BMECは全ての細胞が緑色蛍光を発するSD-Tg(CAG-EGFP)ラットから採取して培養したものを、MSCはラット骨髄から採取して培養し、蛍光試薬PKH26で標識したものをそれぞれ用いた。細胞培養インサート(メンブレンのポアサイズは8.0μm)にBMECを播種し、インサートのlowerチャンバーに10%牛胎仔血清を加えた条件下、upperチャンバーにMSC(1.5×10^4cells/cm^2)を加え、24時間後に固定して観察した。BMECの形態や単層構造に顕著な変化は認められない一方で、BMEC層を通過し、BMEC下にてメンブレン上に接着したMSCが多数観察された。また、ポアを通過してメンブレンの裏側に接着したMSCも認められた。MSCがどのようにBMEC層を通過するのかを明らかにするために、タイムラプスイメージングにより両細胞の動態を観察した。その結果、MSCが傍...
  文部科学省, 挑戦的萌芽研究, 北海道大学, Principal investigator, Competitive research funding, 21659016
• 脳細胞傷害時のグリア活性化におけるToll-like受容体系モーダルシフトの役割
  科学研究費補助金(特定領域研究)
  2009 - 2010
  南 雅文; 片山 貴博
  通常は細胞内に存在する核タンパク質HMGB1や核酸RNAが、細胞傷害時に細胞外に遊離・漏出して細胞間情報伝達分子として働き、一方で、本来は細菌等由来の外来性分子に対するセルセンサーであるToll-like receptor (TLR)がHMGB1やRNAなどの内在性分子に対するセルセンサーとして機能するという「セルセンサーとその適刺激(リガンド)のデュアルモーダルシフト」が、脳細胞傷害によるグリア細胞活性化に関与する可能性について検討した。ラット大脳皮質線条体領域から作製したスライス培養系を用い、アストロサイトの活性化をケモカインMCP-1の産生を指標として評価した検討から、傷害を受けた神経細胞に由来するHMGB1がアストロサイトでのMCP-1産生亢進を引き起こす細胞間情報伝達分子の1つとして機能している可能性を示唆するデータを昨年度の研究で得ている。今年度は、細胞外に漏出するRNAに着目して検討を行った。脳スライス培養系において、NMDAによる神経細胞傷害により、細胞外RNA濃度は著しく上昇した。NMDA誘発神経細胞傷害によって誘導されるアストロサイトでのMCP-1産生は、RNaseAを培地中に加えることによって部分的ながら有意に抑制された。また、細胞外RNAの受容体として機能すると考えられているTLR3のアゴニストpoly I:CによってもアストロサイトでのMCP-1の発...
  文部科学省, 特定領域研究, 北海道大学, Principal investigator, Competitive research funding, 21026001
• 神経細胞傷害時のアストロサイト活性化におけるセルセンサー分子の役割
  科学研究費補助金(特定領域研究)
  2007 - 2008
  南 雅文; 片山 貴博
  我々はこれまでに、ラットの大脳皮質線条体領域から作製した脳スライス培養系を用いた研究から、NMDA処置による神経細胞の特異的傷害が、アストロサイトにおいてケモカインMCP-1の産生を惹起することを明らかにしているが、本研究において、他のケモカインCINC-1に関しても、NMDAによる神経細胞傷害時にアストロサイトにおいてその産生が亢進し、このCINC-1産生に、MCP-1同様、アストロサイトでのMEK-ERK系の活性化が重要であることを明らかにした。一方、近年、DNA結合タンパクHMGB1が、細胞傷害時に細胞外に遊離され細胞間情報伝達を担う因子として注目されている。脳スライス培養系において、HMGB1は、神経細胞、アストロサイト、ミクログリアいずれの細胞の核でも認められるが、NMDA処置後、神経細胞におけるHMGB1免疫活性は消失し、一方で培地中HMGB1量は著しく増加した。次に、HMGB1がサイトカイン・ケモカイン類のmRNA発現に及ぼす影響を検討した。その結果、リコンビナントHMGB1処置によって、その濃度依存的に神経栄養因子の1つであるBDNFのmRNA発現が有意に低下することが明らかとなった。また、HMGB1の受容体として働くと考えられているTLR2、TLR4、RAGEの発現を脳スライス培養系において検討したところ、これら3種の受容体全てのmRNA発現が確認された。以...
  文部科学省, 特定領域研究, 北海道大学, Principal investigator, Competitive research funding, 19045001
• The role of nitrosylation of neurotransmitter transporterin pain-induced aversion
  Grants-in-Aid for Scientific Research(基盤研究(B))
  2007 - 2008
  Masabumi MINAMI; 上原 孝; 片山 貴博; Takashi UEHARA; Takahiro KATAYAMA
  本研究では、痛みによる不安や抑うつ、嫌悪などの不快情動の生成・制御メカニズムを明らかにするため、分界条床核の役割に関して研究を進め、腹側分界条床核におけるノルアドレナリン遊離亢進とβアドレナリン受容体-アデニル酸シクラーゼ-proteinkinase A(PKA)系活性化が痛みによる不快情動生成に重要な役割を果たしていることを明らかにした。一方、ノルアドレナリントランスポーターの酸化的修飾は、その機能に影響を与えなかった。
  Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Principal investigator, Competitive research funding, 19390149
• Roles of plastic changes in glutamate transporter function within the spinal cord in neuropathic pain
  Grants-in-Aid for Scientific Research(基盤研究(C))
  2007 - 2008
  Masanori YAMAUCHI; 南 雅文; Masabumi MINAMI
  グルタミン酸トランスポーター酸化的修飾の神経因性疼痛への関与を明らかにすることを目的として研究を行った。グルタミン酸トランスポーター阻害薬のラット髄腔内投与は、熱性痛覚過敏および機械的アロディニアを惹起した。グルタミン酸トランスポーターの酸化的修飾による活性変化を検討したところ、グルタミン酸トランスポーターGLT-1が酸化的修飾されることが示されたが、酸化的修飾による取り込み活性変化は認められなかった。
  Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(C), 札幌医科大学, Coinvestigator not use grants, Competitive research funding, 19603010
• リアルタイム観察法を駆使した神経細胞傷害によるグリア細胞活性化機構の解明
  科学研究費補助金(特定領域研究)
  2006 - 2007
  南 雅文; 片山 貴博
  神経細胞傷害時におけるミクログリアの傷害部位への集積に関して、Iba1-EGFPトランスジェニックマウス(本特定領域研究班の高坂新一先生より供与を受けた)より作製した培養海馬スライスを用いて検討した。昨年度の検討により、局所組織傷害急性期のミクログリア突起伸長にはATPが関与するが、NMDAによる神経細胞傷害後3〜6日において観察される錐体細胞層へのミクログリア集積にはATPは関与しないことが示された。本年度は、神経細胞傷害後のミクログリアによる傷害細胞の貪食に関して検討した。傷害細胞は、propidium iodide(PI)の核内への取り込みにより可視化した。NMDA処置後、PI陽性細胞数は1〜2日後をピークとして増加し、その後、次第に減少することが明らかとなった。リアルタイムイメージングによる検討から、PI陽性細胞が、1つのミクログリアによって取り囲まれた後に消失することが観察された。さらに、ミクログリア毒であるclodronateをあらかじめ処置することで約90%のミクログリアを除去した培養スライスでは、対照群と比較してPI陽性細胞の減少が著しく抑制された。これらのことから、NMDA処置後のPI陽性細胞の減少は、ミクログリアによる貪食の結果であることが示唆された。このミクログリアの貪食作用におけるP2Y6受容体情報伝達の関与を検討するため、UDPとその分解酵素阻害薬A...
  文部科学省, 特定領域研究, 北海道大学, Principal investigator, Competitive research funding, 18053002
• 脳スライス培養系を用いた神経-グリア-内皮細胞連関におけるケモカイン分子機能解析
  科学研究費補助金(萌芽研究)
  2006 - 2007
  南 雅文; 片山 貴博
  脳は、神経細胞、アストロサイト、ミクログリア、脳微小血管内皮細胞(Brain Microvascular Endothelial Cell;BMEC)など多種の細胞で構成されており、これら細胞間のクロストークにより、BMEC間のタイトジャンクションを基盤としたBBB特有のバリア機能が形成・調節されている。本研究では、神経細胞傷害時における神経-グリア-BMEC間の相互作用によるBBB機能変化のメカニズムを詳細に解析するための実験系として、神経-アストロサイト共培養系とBMECを、多孔質膜を隔てて配置したin vitro BBBモデルを確立した。神経-アストロサイト-BMEC共培養モデルでは、BMEC単独培養系及びアストロサイト-BMEC共培養系よりもTEERが高く、BMEC単独培養系よりもFITC-dextranの透過性が低かったことから、作製したBBBモデルがBMEC単独培養系やアストロサイト-BMEC共培養系よりも高いバリア機能を有していることが示された。また、NMDA処置後48時間以降にTEERの有意な減少とFD40透過性の増大が見られたことから本BBBモデルは、傷害された神経細胞とBMECとの相互作用あるいは神経細胞傷害により活性化したアストロサイトとBMECとの相互作用によるBBB機能変化のメカニズム解明に応用できる実験系であることが示唆された。さらに、NMDAによ...
  文部科学省, 萌芽研究, 北海道大学, Principal investigator, Competitive research funding, 18659014
• Roles of spinal astrocyte in the induction and maintenance of chronic pain
  Grants-in-Aid for Scientific Research(基盤研究(C))
  2006 - 2007
  Takayuki NAKAGAWA; 南 雅文
  We have investigated the roles of spinal astrocytes in chronic pain. Intrathecal administration of ATP to rats produced short-lasting hyperalgesia (<20 min) and subsequently long-lasting allodynia, which appeared within 5 min, reached a plateau between 15 and 30min and lasted fm 3-4 weeks. In the spinal cord, intrathecal ATP administration caused microglia activation within 1 day (induction phase) and subsequently astrocytic activation, which peaked at 1-3 days (transition and early maintenance phase). Taken together with further behavioral studies using inhibitors for microglial and astroc...
  Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(C), 京都大学, Coinvestigator not use grants, Competitive research funding, 18613006
• Molecular pharmacological study on the roles of chemokines in neuropathic pain
  Grants-in-Aid for Scientific Research(基盤研究(C))
  2004 - 2005
  Masabumi MINAMI; 中川 貴之
  Monocyte chemoattractant protein-1(MCP-1,CCL2) is a well-defined CC chemokine implicated in the pathology of various types of brain injuries, such as ischemic and traumatic injuries. Previously, we demonstrated that MCP-1 production was upregulated in the dorsal root ganglia (DRG) of neuropathic pain model rats. In this study, we carried out the double immunofluorescent staining between MCP-1 and activating transcription factor-3(ATF3) to examine whether MCP-1 was produced in the injured or uninjured DRG neurons after the nerve ligation. In the small-sized neurons (cell body area <600 μm^2)...
  Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(C), 京都大学->北海道大学, Principal investigator, Competitive research funding, 16590047
• 脳内ケモカインによるグリア-ニューロン機能連関の時間的・空間的調節機構の解明
  科学研究費補助金(特定領域研究)
  2004 - 2005
  南 雅文; 中川 貴之
  前年度の研究において、大脳皮質-線条体培養切片において、ATPγS処置によるアストロサイトでのMCP-1産生・遊離亢進に対する各種MAPキナーゼ阻害薬の効果について検討したところ、ATPγSによるMCP-1産生・遊離亢進には、MEK/ERKカスケードの活性化が重要な働きをしていることが明らかとなった。さらに、NMDAによる神経細胞傷害により惹起されるアストロサイトでのMCP-1産生・遊離亢進についても各種MAPキナーゼ阻害薬を用いた同様の検討により、、MEK/ERKカスケード活性化が重要であることが示された。そこで、NMDAによる神経細胞傷害時のMEK/ERKカスケード活性化をERKリン酸化亢進を指標として検討したところ、NMDA処置30分以内の早い時間帯では神経細胞において、1時間以後の遅い時間帯ではアストロサイトにおいてERKリン酸化の亢進が観察された。NMDA処置終了後3時間の時点でのMEK阻害薬の添加によってもMCP-1産生・遊離亢進が抑制されたことから、アストロサイトでのMEK/ERKカスケード活性化が重要であることが示唆された。前年度に構築した、神経-グリア共培養系中のアストロサイトにEGFPを発現させることによりアストロサイト形態を経時的に観察することが可能な実験系を用いて、NMDA処置による神経細胞傷害時のアストロサイト形態変化におけるMEK/ERKカスケード...
  文部科学省, 特定領域研究, 京都大学->北海道大学, Principal investigator, Competitive research funding, 16047216
• Molecular pharmacological study on the roles of the central noradreneric neurosis in the higher central actions of morphine
  Grants-in-Aid for Scientific Research(基盤研究(B))
  2002 - 2003
  Masamichi SATOH; 中川 貴之; 南 雅文
  μ-Opioid receptor, a receptor far morphine, is intensely expressed in the noradrenergic neurons located in the locus coeruleus.. These neurons project into various brain regions including the cerebral cortex, hippocampus and amygdala, and are implicated in memory, emotion and stress responses. However, the molecular bases for the regulation of memory, emotion and stress responses through the opioid system remain to be elucidated. In this study, we generated the genetically modified mouse line in which μ-opioid receptors are expressed only in the not adrenergic neurons by means of the crossb...
  Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 京都大学, Coinvestigator not use grants, Competitive research funding, 14370743
• モルヒネの分子作用機構解析のための神経細胞種特異的なオピオイド受容体発現動物作製
  科学研究費補助金(萌芽研究)
  2002 - 2003
  佐藤 公道; 中川 貴之; 南 雅文
  モルヒネの鎮痛作用機序として、延髄諸核からの下行性抑制系の賦活化や一次感覚神経終末からの伝達物質遊離抑制が重要であるが、これらの作用機序の各々が、全身性に投与されたモルヒネによる個体レベルでの鎮痛作用発現にどの程度の割合で寄与しているかは明らかでない。また、精神的薬物依存に深く関与する中脳ドパミン神経系賦活化は、抑制性GABA作動性神経を抑制することによる「脱抑制」によることが、これまでの薬理学的・電気生理学的研究により示唆されているが、分子レベルにまで踏み込んだ研究成果は報告されていない。身体的依存形成における青斑核ノルアドレナリン神経系の関与についても同様である。そこで、これらの問題に対し分子レベルでの解答を得るため、一次感覚神経、GABA神経系およびノルアドレナリン神経系、それぞれの神経系にだけ特異的にμオピオイド受容体を発現する遺伝子改変マウスの作製を着想するに至った。本研究では、ノルアドレナリン神経特異的プロモーターであるdopamine-β-hydroxylaseプロモーター下にμオピオイド受容体を発現するトランスジェニックマウスとμオピオイド受容体ノックアウトマウスをかけ合わせることにより、ノルアドレナリン神経のみでμオピオイド受容体を発現する遺伝子改変マウスの作製を行った。本遺伝子改変マウスにおいてモルヒネの有意な鎮痛作用は認められなかった。一方、tail-s...
  文部科学省, 萌芽研究, 京都大学, Coinvestigator not use grants, Competitive research funding, 14657024
• Roels of chemokines in ischemic brain injury
  Grants-in-Aid for Scientific Research(基盤研究(C))
  2001 - 2002
  Masabumi MINAMI; 名村 尚武
  Production of chemokines and their receptors in the brain has been reported under various pathological conditions. In this study, we showed that intracerebroventricular and intravenous injections of TAK-779, a CCR2/ CCR5 selective chemokine receptor antagonist, reduced infarct volume. Furthermore, intravenous injection of TAK-779 decreased the number of activated macrophages/microglia, but not that of neutrophils, in the ischemic penumbra. These findings suggest that brain chemokines play a crucial role in ischemic injury, at least in part, by enhancing the leukocyte infiltration and microg...
  Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(C), 京都大学, Principal investigator, Competitive research funding, 13672280
• オピオイド受容体遺伝子導入による痛覚情報伝達制御
  科学研究費補助金(萌芽的研究)
  2001 - 2001
  佐藤 公道; 中川 貴之; 南 雅文
  神経因性疼痛では、本来は侵害情報を伝達しないAβ線維が非侵害情報を侵害情報として伝達するように変化している可能性が示唆されている。本来は非侵害性情報伝達を担うAβ線維などは、オピオイド受容体を介した痛覚情報伝達抑制系を有していない可能性が高く、また、正常時にはそのような抑制系を有しているAδやC線維においても、神経因性疹痛の病態時にオピオイド受容体を介した抑制系がダウンレギュレーションされていることが考えられ、そのことが、神経因性疼痛においてモルヒネなどの麻薬性鎮痛薬が効きにくい理由である可能性が考えられる。そのような病態時においては、ウイルスベクターによる1次感覚神経細胞へのオピオイド受容体遺伝子導入が、麻薬性鎮痛薬に対する感受性を向上させ、麻薬性鎮痛薬による神経因性疼痛治療を可能にすることが期待される。本研究では、「オピオイド受容体遺伝子導入による神経因性疼痛の新しい治療法開発上を目指した研究の予備的研究として、ヘルペスウイルスベクターにより1次感覚神経細胞に高効率にオピオイド受容体遺伝子を発現させ、導入したオピオイド受容体を介してモルヒネ鎮痛効果の増強を得ることを目的とした。μオピオイド受容体遺伝子を組み込んだアンプリコンプラスミドを作成し、μオピオイド受容体遺伝子導入に用いるヘルペスウイルスベクター(通常の動物細胞での増殖性をなくしたヘルペスウイルス)を作製した。本ウ...
  文部科学省, 萌芽的研究, 京都大学, Coinvestigator not use grants, Competitive research funding, 13877013
• Pharmacological study on the role of amygdala in sensory and affective components of pain
  Grants-in-Aid for Scientific Research(基盤研究(B))
  2000 - 2001
  Masamchi SATOH; 宮武 伸一; 中川 貴之; 南 雅文; 佐治 英郎
  We investigated the role of the amygdala in sensory and negative affective components of the pain experience in rats. We found that somatic noxious stimulus by intraplanter injection of formalin increased c-fos mRNA expression in lateral (LaA) and basolateral (BLA) nuclei of the amygdala, while visceral noxious stimulus by intraperitoneal injection of acetic acid induced c-fos mRNA especially in the central nucleus of the amygdala (CeA). Both somatic and visceral noxious stimuli produced aversive avoidance behavior from the environment associated with them (conditioned place aversion (CPA))...
  Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 京都大学, Coinvestigator not use grants, Competitive research funding, 12470498
• Development of nonpeptidic opioid PET ligands to study pain system in the higher brain
  Grants-in-Aid for Scientific Research(基盤研究(B))
  2000 - 2001
  Masamchi SATOH; 中川 貴之; 南 雅文; 佐治 英郎; 岩村 樹憲
  μ-Opioid receptors and their endogenous ligand are involved in the regulation of sensory and affective components of the pain experience. However, the molecular basis of the roles of opioidergic system in the higher brain functions, such as emotion and memory, remains to be elucidated. In this study, we studied on the synthesis and structure-activity relationships μ-opioid ligand to develop novel μ-selective nonpeptidic ligands which can be used for the positron emission tomography (PET) study. We synthesized several 1-aralky-4-phenylaminopiperidinecarboxylate derivatives and examined the b...
  Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 京都大学, Coinvestigator not use grants, Competitive research funding, 12557230
• Roles of fractalkine in neuron-microglia interaction at brain injury
  Grants-in-Aid for Scientific Research(基盤研究(C))
  1999 - 2000
  Masabumi MINAMI; 宮武 伸一
  Fractalkine is a novel chemokine which has a CX3C motif and a membrane-bound form. We previously reported that, in the rat brain, fractalkine mRNA was expressed in neurons while the mRNA for its receptor (CX3CR1) was in microglia. This finding suggests that fractalkine possibly plays an important role to convey the information from neurons to microglia. To examine the role if fractalkine in neuron-microglia interaction at brain injury, we investigated the expression of fractalkine and its receptor CX3CR1 and the effect of exogenous fractalkine on neuronal cell death and microglia activation...
  Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(C), 京都大学, Principal investigator, Competitive research funding, 11672167
• 脳内グリア細胞活性化におけるケモカインの役割に関する分子薬理学的研究
  科学研究費補助金(奨励研究(A))
  1997 - 1998
  南 雅文
  脳虚血/再灌流負荷により、MCP-1およびMIP-1αmRNAともに脳内での発現が観察されたが時間経過及び発現分布は異なっていた。MCP-1mRNAは、再灌流2時間から24時間後で強い発現が主に虚血辺縁部に見られ、48時間後では虚血中心部を含む広い範囲に発現が観察された。MCP-1mRNAはMac-1α陽性のミクログリアと考えられる細胞およびGFAP陽性のアストロサイトと考えられる細胞の両方で発現が観察された。一方、MIP-1αmRNA発現のピークは再灌流4時間後で、その後、徐々に減弱するシグナルが24時間後まで観察された。発現は主に虚血辺縁部で見られ、シグナルはMac-1α陽性細胞でのみ観察された。培養ミクログリアに種々の神経伝達物質を処置し、MCP-1mRNAの発現を検討したところATP処置により顕著な発現増加が見られた。ATP処置によりMIP-1αmRNAの発現も顕著に増大した。MCP-1およびMIP-1αmRNA発現は、LPS処置によっても顕著に増大した。培養アストロサイトでは、MCP-1mRNAの発現がインターロイキン-1(IL-1)により顕著に増加した。MIP-1αmRNA発現は未処置およびIL-1処置いずれのアストロサイトでも検出されなかった。一方、LPS処置ではMCP-1およびMIP-1αmRNAともに発現が誘導された。本研究により、脳虚血により脳内グリア細胞...
  文部科学省, 奨励研究(A), 京都大学, Principal investigator, Competitive research funding, 09771980
• Study on the molecular mechanisms for neuronal plasticicity in the drug dependence
  Grants-in-Aid for Scientific Research(基盤研究(B))
  1997 - 1998
  Masamchi SATOH; 南 雅文; 佐治 英郎; 中川 貴之
  We investigated the molecular mechanism responsible for supersensitization of the AC system induced by sustained opioid treatment using CHO cells expressing one of the cloned opioid receptors. In cells treated for 4 h with opioid agonists, challenge with opioid antagonists induced supersensitization of the AC system over the naive level, but had no effect on GTPase activity. This phenomenon was not affected by cycloheximide. To examine the involvement of the interaction between G-protein and AC in the development of supersensitization, we used CHO cells co-expressing the opioid receptor and...
  Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 京都大学, Coinvestigator not use grants, Competitive research funding, 09470503
• Ligand design for orphan receptors by the modeling with stepwise mutated receptors
  Grants-in-Aid for Scientific Research(基盤研究(B))
  1997 - 1998
  Masamchi SATOH; 長瀬 博; 南 雅文; 中川 貴之
  The nociceptin receptor was firstly cloned as an opioid receptor-like orphan receptor. Recently, nociceptin (orphanin FQ) has been isolated as an endogenous peptidic ligands of this orphan receptor, but the physiological and pathological roles of nociceptin have not been elucidated.To obtain useful information about creating nonpeptidic ligands of the nociceptin receptor, we investigated the molecular mechanism of the discrimination by bremazocine, a nonpeptidic opioid ligand, between opioid receptors and nociceptin receptor, by constructing chimeric and mutated nociceptin receptors. We rev...
  Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 京都大学, Coinvestigator not use grants, Competitive research funding, 09557193
• 神経-グリア-内皮細胞連関におけるインターロイキン-1の役割
  科学研究費補助金(奨励研究(A))
  1996 - 1996
  南 雅文
  内皮細胞由来の血管弛緩因子として知られているエンドセリンの処置により、培養アストロサイトにおける1型インターロイキン-1受容体mRNAの発現が増加することをノーザンブロット法を用いて明らかにした。また、インターロイキン-1のアストロサイトに対する作用として、アストロサイトの増殖促進作用のあることが明らかとなった。また、培養ミクログリア細胞におけるインターロイキン-1βの発現調節機構を検討した結果、インターロイキン-1βmRNAの発現が、ATPおよびβアドレナリン受容体アゴニストであるイソプロテレノールにより誘導されることが明らかとなった。また、1型インターロイキン-1受容体が脳の特定領域の神経細胞および脳微小血管の内皮細胞で発現していることを以前の研究により明らかにしているが、本研究において、2型インターロイキン-1受容体が、正常ラット脳内ではほとんど発現していないが、興奮性神経毒であるカイニン酸の投与により脳の特定領域の神経細胞および脳微小血管の内皮細胞で発現誘導されることを新たに見いだした。以上の知見より、脳虚血あるいは興奮性神経毒による神経細胞の異常興奮あるいは損傷により、神経細胞からアドレナリン/ノルアドレナリンやATPなどの生理活性物質が遊離あるいは漏出され、それらがミクログリアに作用することによりインターロイキン-1の発現が誘導され、産生されたインターロイキン-1...
  文部科学省, 奨励研究(A), 京都大学, Principal investigator, Competitive research funding, 08772088
• 分子モデリングによるorphan受容体のリガンドデザインのための基礎的研究
  科学研究費補助金(萌芽的研究)
  1996 - 1996
  佐藤 公道; 南 雅文
  オピオイド受容体における受容体-リガンド認識機構を分子レベルで解析した。オピオイド受容体μタイプに選択的なリガンドであるDAMGOのμ/δ受容体間識別に、第1細胞外ループと第2膜貫通部位の境界領域に存在するμ受容体127番目のアスパラギン残基とδ受容体の対応する位置に存在する108番目のリジン残基の違いが重要であることを明らかにした。また、DAMGOのμ/κ受容体間識別には、第3細胞外ループと第6膜貫通部位の境界領域に存在するμ受容体303番目のリジン残基とκ受容体の対応する位置に存在する297番目のグルタミン酸残基の違い、および、第3細胞外ループと第7膜貫通部位の境界領域に存在するμ受容体316番目のバリン、318番目のトリプトファン、319番目のヒスチジンとκ受容体の対応する位置に存在する310番目のセリン、312番目のチロシン、313番目のチロシンの違いが重要であることを明らかにした。さらに、オピオイド受容体と非常に高い相同性を有するにもかかわらず、オピオイドリガンドが結合しないことが知られているOrphaninFQ受容体の非ペプチド性リガンドを合理的にデザインするための基礎的知見を得ることを目的として、オピオイドリガンドがOrphaninFQ受容体に結合できない原因となっている受容体構造の解明を試みた結果、OrphaninFQ受容体の第2細胞外ループと第5膜貫通部位の...
  文部科学省, 萌芽的研究, 京都大学, Coinvestigator not use grants, Competitive research funding, 08877327
• Molecular pharmacological study on he roles of brain cytokines in narcotic dependence
  Grants-in-Aid for Scientific Research(一般研究(B), 基盤研究(B))
  1995 - 1996
  Masamichi SATOH; 南 雅文
  Intracisternal injection of interleukin-1beta was shown to suppress naloxone-precipitated with-drawal syndrome in morphine dependent mouse. This effect of interleukin-1beta was mediated by CRF and prostaglandin E2. In order to clarify the target cells for interleukin-1beta in the brain, we visualized the cells expressing type 1 and type 2 interleukin-1 receptors using an in situ hybridization technique. In morphine-dependent mouse, prostaglandin E2 suppressed the withdrawal syndrome through EP3 receptors. Prostaglandin EP3 agonists suppressed the withdrawal syndrome also in the morphine-dep...
  Ministry of Education, Culture, Sports, Science and Technology, 一般研究(B), 基盤研究(B), 京都大学, Coinvestigator not use grants, Competitive research funding, 07457538
• Visualization and quantification of gene expression involved in pain transmission and regulation with molecular probes
  Grants-in-Aid for Scientific Research(試験研究(B), 基盤研究(A))
  1995 - 1996
  Masamichi SATOH; 南 雅文; 金子 周司
  For the purpose to increase the sensitivity of an in situ hybridization technique with nonradioactive probes, we examined the several methods for nonradioactive labeling of RNA probes. Simiar sensitivities were obtained between digoxigenin- and fluorescein-labeled antisense RNA probes to detect the target mRNA,but the background signals were lower in the results with digoxigenin-labeled probe than with fluorescein-labeled one. For an analysis of the results of double in situ hybridization histochemistry, we developed an apparatus to simultaneously obtain both bright- and dark-field images, ...
  Ministry of Education, Culture, Sports, Science and Technology, 試験研究(B), 基盤研究(A), 京都大学, Coinvestigator not use grants, Competitive research funding, 07557010
• 麻薬依存における脳内プロスタノイド受容体の役割に関する分子薬理学的研究
  科学研究費補助金(奨励研究(A))
  1995 - 1995
  南 雅文
  モルヒネペレットを慢性的に皮下に埋め込むことによりモルヒネに対する依存を形成したマウスにおけるナロキソン誘発禁断症状の1つである跳躍行動が、プロスタグランジンE2受容体のEP3サブタイプアゴニストM&B28,767やsulprostoneの脳室内投与により抑制されることを明らかにした。プロスタグランジン受容体のEP1/IPアゴニストiloprost、EP2アゴニストbutaprost、EPアゴニストprostaglandinF2aの脳室内投与は跳躍行動抑制効果を示さなかった。EP3アゴニストの脳室内投与は跳躍行動以外にも、paw shakeや体重減少などの禁断症状を抑制した。また、マウスに比べて多数の項目を観察することが容易であるラットを用いた実験においても、プロスタグランジンEP3受容体アゴニスト脳室内投与により、跳躍行動やpaw shakeなどの禁断症状が抑制されることを明らかにした。さらに、ラット脳において、麻薬依存形成に深く関与していることが知られている青斑核などの脳部位で、モルヒネの作用部位であるμオピオイド受容体のmRNAとEP3受容体mRNAの両方が発現していることをin situ hybridization法を用いて明らかにした。各受容体をコードするcDNAをin situhybridization法に用いるプローブ作製に適したベクターにサブクローニングする際...
  文部科学省, 奨励研究(A), 京都大学, Principal investigator, Competitive research funding, 07772164
• Molecular biological and pharmacological study on the roles of brain interleukin-1 in transmission and regulation of nociceptive information
  Grants-in-Aid for Scientific Research(一般研究(B))
  1993 - 1994
  Masamichi SATOH; 南 雅文
  In this study, we conducted the following expeiments to elucidate the roles of brain interleukin-1beta in the modulation of nociceptive information. First, IL-1beta was intracerebroventriculary administrated and the nociceptive threshold to mechanical stimulation was measured. The lower doses (10,000 pg) of IL-1beta induced hyperalgesia, but the higher doses (1,10 ng) of IL-1beta induced analgesia. These effects of IL-1beta on the nociceptive threshold were inhibited by the simultaneous administration of IL-1 receptor antagonist.Hyperalgesia induced by the lower dose of IL-1beta but not ana...
  Ministry of Education, Culture, Sports, Science and Technology, 一般研究(B), 京都大学, Coinvestigator not use grants, Competitive research funding, 05454569
• 脳虚血/再灌流時における脳内サイトカイン類の動態に関する分子生物学的研究
  科学研究費補助金(奨励研究(A))
  1993 - 1993
  南 雅文
  サイトカインあるいはその受容体のmRNAの産生細胞を同定する方法として脳を構築する各種細胞のマーカーとなるタンパクあるいは糖鎖にたいする抗体による免疫組織染色とサイトカインあるいはその受容体に対するin situ hybridizationを同一切片上で行うことを試みた。アストロサイトのマーカーであるGFAPに対する抗体を用いた実験により、カイニン酸で発現が誘導されるIL-1betamRNAの産生細胞はGFAP陰性のグリア細胞、おそらくは、ミクログリアであることが判明した。さらに、4血管閉塞モデルおよび中大脳動脈閉塞モデルによる脳虚血によっても脳内でIL-1betamRNAがグリア細胞と考えられる細胞および血管内皮細胞で発現することを明らかにした。そこで、ミクログリアのマーカーであるMac-1に対する抗体による免疫組織染色とin situ hybridizationによる二重染色を試みたが、GFAPの場合と異なり、抗Mac-1抗体は本方法には適しておらず二重染色することができなかった。そこで、放射性標識したRNAプローブとジゴキシゲニン標識したRNAプローブを用いたin situ hysridizationによる二重染色法を新たに開発した。この方法により、神経細胞のマーカーである神経特異的エノラーゼのmRNAとIL-1受容体type1mRNAが同一の細胞で発現していること、す...
  文部科学省, 奨励研究(A), 京都大学, Principal investigator, Competitive research funding, 05771974
• 痛みに伴う不安・不快等の情動反応の分子機構とその制御
  Competitive research funding
• 中枢神経疾患、神経因性疼痛における脳内サイトカイン・ケモカインの発現と役割
  Competitive research funding
• 脳内におけるサイトカイン・ケモカイン類の発現と機能に関する研究
  Competitive research funding
• Study on the neuronal mechanisms for pain-induced negative emotion
  Competitive research funding
• Study on the expressions and roles of cytokines and chemokines in the brain
  Competitive research funding