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The role of intracellular muscarinic M1 receptor in neuropsychiatric disorders

Research Project

Project/Area Number 16K19023
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General pharmacology
Research InstitutionKanazawa Medical University

Principal Investigator

MASUOKA Takayoshi  金沢医科大学, 医学部, 准教授 (80509307)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsアセチルコリン / 海馬 / LTP / 記憶 / ムスカリン受容体 / 長期増強 / アセチルコリン受容体
Outline of Final Research Achievements

Muscarinic acetylcholine receptors M1 (M1 receptors) regulate cognitive processes including attention, learning and memory in the central nervous system. In the hippocampus and the cerebral cortex, 50% of the M1 receptors are located at Golgi apparatus and endoplasmic reticulum, in addition to the plasma membrane. However, the physiological roles of intracellular M1 receptors remain unclear. In this study, we found that the intracellular M1 receptors activated by endogenous acetylcholine regulate hippocampal longe-term potentiation (LTP) and contribute to learning and memory. The synaptic regulation of intracellular M1 receptors was supressed by chronic stress, suggesting that intracellular M1 receptor might be involved in stressor related mental disorder.

Academic Significance and Societal Importance of the Research Achievements

アセチルコリンは脳機能を調節する重要な神経伝達物質であり、近年ではアルツハイマー病などの記憶学習障害や認知機能障害の治療標的として注目されている。本研究では、脳内アセチルコリンの情報を受け取る受容体の一つであるM1受容体のうち、いままで生理機能が明らかにされていなかった細胞内に存在するM1受容体が、記憶学習の制御に関与していることを示した。本研究成果は、脳内アセチルコリンによる神経伝達機構に関する理解を深め、新規記憶学習障害治療薬の開発に重要な知見を提供するものである。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (32 results)

All 2019 2018 2017 2016

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (24 results) (of which Int'l Joint Research: 8 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Augmentation of endogenous acetylcholine uptake and cholinergic facilitation of hippocampal long-term potentiation by acetylcholinesterase inhibition2019

    • Author(s)
      Masuoka T, Uwada J, Kudo M, Yoshiki H, Yamashita Y, Taniguchi T, Nishio M, Ishibashi T, Muramatsu I
    • Journal Title

      Neuroscience

      Volume: 404 Pages: 39-47

    • DOI

      10.1016/j.neuroscience.2019.01.042

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Persistent activation of histamine H1 receptors in the hippocampal CA1 region enhances NMDA receptor-mediated synaptic excitation and long-term potentiation in astrocyte- and D-serine-dependent manner.2019

    • Author(s)
      Masuoka T, Ikeda R, Konishi S.
    • Journal Title

      Neuropharmacology

      Volume: 151 Pages: 64-73

    • DOI

      10.1016/j.neuropharm.2019.03.036

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel regulatory systems for acetylcholine release in rat striatum and anti‐Alzheimer's disease drugs2019

    • Author(s)
      Muramatsu Ikunobu、Uwada Junsuke、Yoshiki Hatsumi、Sada Kiyonao、Lee Kung‐Shing、Yazawa Takashi、Taniguchi Takanobu、Nishio Matomo、Ishibashi Takaharu、Masuoka Takayoshi
    • Journal Title

      Journal of Neurochemistry

      Volume: 印刷中 Issue: 5 Pages: 605-623

    • DOI

      10.1111/jnc.14701

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Inhibitory effect of amitriptyline on the impulse activity of cold thermoreceptor terminals of intact and tear-deficit guinea pig corneas2018

    • Author(s)
      Takayoshi Masuoka, Juana Gallar, Carlos Belmonte.
    • Journal Title

      J Ocul Pharmacol Ther.

      Volume: 34 Issue: 1-2 Pages: 195-203

    • DOI

      10.1089/jop.2017.0066

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of synaptic acetylcholine concentrations by acetylcholine transport in rat striatal cholinergic transmission2017

    • Author(s)
      Muramatsu Ikunobu、Uwada Junsuke、Masuoka Takayoshi、Yoshiki Hatsumi、Sada Kiyonao、Lee Kung-Shing、Nishio Matomo、Ishibashi Takaharu、Taniguchi Takanobu
    • Journal Title

      Journal of Neurochemistry

      Volume: 143 Issue: 1 Pages: 76-86

    • DOI

      10.1111/jnc.14127

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] TRPA1 channels modify TRPV1-mediated current responses in dorsal root ganglion neurons2017

    • Author(s)
      Takayoshi Masuoka, Makiko Kudo, Yuka Yamashita, Junko Yoshida, Noriko Imaizumi, Ikunobu Muramatsu, Matomo Nishio, Takaharu Ishibashi.
    • Journal Title

      Frontiers in Physiology

      Volume: 8 Pages: 272-272

    • DOI

      10.3389/fphys.2017.00272

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Pharmacological evidence of specific acetylcholine transport in rat cerebral cortex and other brain regions.2016

    • Author(s)
      Ikunobu Muramatsu, Hatsumi Yoshiki, Junsuke Uwada, Takayoshi Masuoka, Kiyonao Sada, Takanobu Taniguchi, Matomo Nishio.
    • Journal Title

      Journal of Neurochemistry

      Volume: 139 Issue: 4 Pages: 566-575

    • DOI

      10.1111/jnc.13843

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 慢性的な涙液欠乏は角膜の冷感受性神経におけるTRPV1を介した発火活動を感作する2019

    • Author(s)
      山下優香、益岡尚由、橋川成美、中野克哉、田和正志、西尾眞友、村松郁延、石橋隆治
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] タバコ煙抽出液を慢性投与したラット血管における可溶性グアニル酸シクラーゼ酸化還元状態2019

    • Author(s)
      田和正志、山下優香、中野克哉、西尾眞友、益岡尚由、石橋隆治
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Contribution of intracellular acetylcholine receptor to hippocampal long-term potentiation2018

    • Author(s)
      Takayoshi Masuoka, Makiko Kudo, Matomo Nishio, Ikunobu Muramatsu, Takaharu Ishibashi
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nerve growth factor facilitates metabotropic glutamate receptor agonist-induced calcium elevation in dorsal root ganglion neurons2018

    • Author(s)
      Takayoshi Masuoka, Yuka Yamashita, Junko Yoshida, Masashi Tawa, Matomo Nishio, Takaharu Ishibashi
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A new aspect of cholinergic transmission in central nervous system2018

    • Author(s)
      Ikunobu Muramatsu, Takayoshi Masuoka, Matomo Nishio, Takaharu Ishibashi
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SEX DIFFERENCES IN RELAXANT RESPONSES OF RAT AORTAS TO CGMP GENERATORS2018

    • Author(s)
      Ishibashi T., Tawa M., Yamashita Y. and Masuoka T.
    • Organizer
      10th International Conference on the Biology, Chemistry and Therapeutic Applications of Nitric Oxide
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Chronic ocular dryness sensitizes TRPV1 on corneal cold sensitive nerves2018

    • Author(s)
      Takayoshi Masuoka, Yuka Yamashita, Masashi Tawa, Matomo Nisio, Ikunobu Muramatsu, Takaharu Ishibashi.
    • Organizer
      Society for Neuroscience
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel aspect of cholinergic transmission in central nervous system2018

    • Author(s)
      Ikunobu Muramatsu, Takayoshi Masuoka, Matomo Nisio, Takaharu Ishibashi.
    • Organizer
      Society for Neuroscience
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 可溶性グアニル酸シクラーゼ刺激を介する血管弛緩反応は酸化的修飾により変化する2018

    • Author(s)
      田和 正志、山下 優香、益岡 尚由、吉田 純子、西尾 眞友、石橋 隆治
    • Organizer
      第71回日本酸化ストレス学会・第18回日本NO学会合同学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 角膜神経のカプサイシン感受性に対する涙腺摘出の影響2018

    • Author(s)
      益岡 尚由、山下 優香、田和 正志、西尾 眞友、村松郁延、石橋 隆治
    • Organizer
      第133回日本薬理学会近畿部会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 神経成長因子による代謝型グルタミン酸受容体の機能変化を引き起こす分子機構の解析2018

    • Author(s)
      益岡 尚由、山下 優香、田和 正志、村松郁延、西尾 眞友、石橋 隆治
    • Organizer
      第22回活性アミンに関するワークショップ
    • Related Report
      2018 Annual Research Report
  • [Presentation] バルーン傷害血管における可溶性グアニル酸シクラーゼの酸化還元状態2018

    • Author(s)
      田和 正志、下里 貴、左近上 博司、益岡 尚由、西尾 眞友、石橋 隆治、岡村 富夫
    • Organizer
      第28回日本循環薬理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 知覚・痛覚から見たドライアイについて2018

    • Author(s)
      益岡尚由
    • Organizer
      第122回日本眼科学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 炎症による代謝型グルタミン酸受容体アゴニスト誘発痛覚行動の増強における神経成長因子の関与2017

    • Author(s)
      益岡尚由、工藤麻希子、吉田純子、山下優香、今泉範子、西尾眞友、石橋隆治
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール(長崎県長崎市)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
  • [Presentation] 炎症性疼痛における末梢性グルタミン酸受容体の機能亢進とその作用機序の解析2017

    • Author(s)
      益岡尚由、山下優香、吉田純子、村松郁延、田和正志、西尾眞友、石橋隆治
    • Organizer
      第21回活性アミンに関するワークショップ
    • Related Report
      2017 Research-status Report
  • [Presentation] 中枢におけるコリン伝達機構の新しいメカニズム2017

    • Author(s)
      村松郁延、益岡尚由、西尾眞友、石橋隆治
    • Organizer
      第21回活性アミンに関するワークショップ
    • Related Report
      2017 Research-status Report
  • [Presentation] 侵害受容性神経に発現する代謝型グルタミン酸受容体の炎症による機能変化2017

    • Author(s)
      益岡尚由、山下優香、吉田純子、村松郁延、田和正志、西尾眞友、石橋隆治
    • Organizer
      第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 可溶性グアニル酸シクラーゼの酸化的修飾と cGMP 産生薬による血管反応性2017

    • Author(s)
      田和正志、山下優香、益岡尚由、吉田純子、西尾眞友、石橋隆治
    • Organizer
      第 132 回日本薬理学会近畿部会
    • Related Report
      2017 Research-status Report
  • [Presentation] cGMP 産生薬に対する血管の応答性:チオール酸化剤あるいはヘム鉄酸化剤の影響2017

    • Author(s)
      田和正志、山下優香、益岡尚由、吉田純子、西尾眞友、石橋隆治
    • Organizer
      第 27 回日本循環薬理学会
    • Related Report
      2017 Research-status Report
  • [Presentation] TRPA1 channel modifies membrane current induced by TRPV1 channels activation in dorsal root ganglion neurons.2016

    • Author(s)
      Takayoshi Masuoka, Makiko Kudo, Takaharu Ishibashi, Matomo Nishio
    • Organizer
      Society for Neuroscience 2016
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 神経成長因子による知覚神経のグルタミン酸受容体機能変化2016

    • Author(s)
      益岡尚由、吉田純子、工藤麻希子、今泉範子、西尾眞友、石橋隆治
    • Organizer
      第67回日本薬理学会北部会
    • Place of Presentation
      北海道大学学術交流会館(北海道札幌市)
    • Year and Date
      2016-09-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Possible contribution of glutamate receptors in ocular hyperalgesia2016

    • Author(s)
      Takayoshi Masuoka, Takaharu Ishibashi, Matomo Nishio
    • Organizer
      XXI Biennial Meeting of International Society for Eye Research
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 中枢におけるコリン作動性伝達機構2016

    • Author(s)
      村松郁延、吉木はつみ、宇和田淳介、益岡尚由、定清直、谷口隆信、西尾眞友
    • Organizer
      第18回応用薬理シンポジウム
    • Place of Presentation
      名古屋大学医学部(愛知県名古屋市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 中枢における新規アセチルコリン伝達機構2016

    • Author(s)
      村松郁延、吉木はつみ、宇和田淳介、益岡尚由、定清直、谷口隆信、西尾眞友
    • Organizer
      第20回活性アミンに関するワークショップ
    • Place of Presentation
      ホテルマークワンつくば研究学園(茨城県つくば市)
    • Year and Date
      2016-08-20
    • Related Report
      2016 Research-status Report
  • [Book] A New Aspect of Cholinergic Transmission in the Central Nervous System. In Akinori Akaike, Shun Shimohama, Yoshimi Misu eds. Nicotinic Acetylcholine Receptor Signaling in Neuroprotection2018

    • Author(s)
      Ikunobu Muramatsu, Takayoshi Masuoka, Junsuke Uwada, Hatsumi Yoshiki, Takashi Yazama, Kung-Shing Lee, Kiyonao Sada, Matomo Nishio, Takaharu Ishibashi, Takanobu Taniguchi.
    • Publisher
      Springer
    • ISBN
      9789811084881
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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