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Visualization of disrupted glutamate dynamics in the brain upon psychiatric disorders

Research Project

Project/Area Number 16K08543
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionThe University of Tokyo

Principal Investigator

Okubo Yohei  東京大学, 大学院医学系研究科(医学部), 講師 (40422282)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords統合失調症 / うつ / グルタミン酸 / 脳・神経 / 薬理学 / うつ病
Outline of Final Research Achievements

Although disruption of glutamate dynamics in the brain is atracting attention as a cause of psychiatric disorders, many points remain elusive. We thus set out to apply our unique glutamate fluorescence imaging technique for psychiatric disorders including schizophrenia and depression, and tried to clarify the disrupted glutamate dynamics and its mechanism in the brain. We for the first time found a spontaneous and spatially confined increase in glutamate concentration in the cerebral cortex. Since this glutamate dynamics was observed even under the inhibition of neuronal activity, release from glial cells, in particular astrocytes, was expected. It is expected to be a factor of non-neural factor for the disruption of glutamate dynamics in the pathological condition, and further analysis of the mechanism and elucidation of the causal relationship are awaited.

Academic Significance and Societal Importance of the Research Achievements

精神疾患のメカニズムは未だ不明な点が多く、既存の治療法は社会的要請を十分に満たしていない。本研究で発見されたグルタミン酸動態を評価軸にして病態や既存薬の効果を解析することで、治療抵抗性の統合失調症やうつ病に対する新たな治療法の開発に資する知見が得られることが期待される。

Report

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

    (19 results)

All 2019 2018 2017 2016 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (12 results) (of which Int'l Joint Research: 5 results,  Invited: 3 results) Remarks (2 results)

  • [Journal Article] Inositol 1,4,5-trisphosphate receptor type 2-independent Ca2+ release from the endoplasmic reticulum in astrocytes2019

    • Author(s)
      Okubo Yohei、Kanemaru Kazunori、Suzuki Junji、Kobayashi Kenta、Hirose Kenzo、Iino Masamitsu
    • Journal Title

      Glia

      Volume: 67 Issue: 1 Pages: 113-124

    • DOI

      10.1002/glia.23531

    • NAID

      130007812856

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Visualization of astrocytic intracellular Ca2+ mobilization2019

    • Author(s)
      Okubo Yohei、Iino Masamitsu
    • Journal Title

      The Journal of Physiology

      Volume: 印刷中 Issue: 9 Pages: 1671-1681

    • DOI

      10.1113/jp277609

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of endoplasmic reticulum-mediated Ca2+ signaling in neuronal cell death2018

    • Author(s)
      Okubo Yohei、Mikami Yoshinori、Kanemaru Kazunori、Iino Masamitsu
    • Journal Title

      Antioxid Redox Signal (in press)

      Volume: - Issue: 12 Pages: 1147-1157

    • DOI

      10.1089/ars.2018.7498

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nitric Oxide-induced Activation of the Type 1 Ryanodine Receptor Is Critical for Epileptic Seizure-induced Neuronal Cell Death2016

    • Author(s)
      Mikami, Y., Kanemaru, K., Okubo, Y., Nakaune, T., Suzuki, J., Shibata, K., Sugiyama, H., Koyama, R., Murayama, T., Ito, A., Yamazawa, T., Ikegaya, Y., Sakurai, T., Saito, N., Kakizawa, S. and Iino, M.
    • Journal Title

      EBioMedicine.

      Volume: 11 Pages: 253

    • DOI

      10.1016/j.ebiom.2016.08.020

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Whisker experience-dependent mGluR signaling maintains synaptic strength in the mouse adolescent cortex.2016

    • Author(s)
      Kubota, J., Mikami, Y., Kanemaru, K., Sekiya, H., Okubo, Y. and Iino, M.
    • Journal Title

      Eur. J. Neurosci.

      Volume: 44 Issue: 3 Pages: 2004-2014

    • DOI

      10.1111/ejn.13285

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] アストロサイトにおけるIP3受容体2型非依存性Ca2+放出2019

    • Author(s)
      大久保 洋平、金丸 和典、鈴木 純二、小林 憲太、廣瀬 謙造、飯野 正光
    • Organizer
      第92回 日本薬理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Visualization of Ca2+ dynamics within the endoplasmic reticulum in neurons and glial cells2019

    • Author(s)
      Yohei Okubo
    • Organizer
      第22回 日韓薬理合同セミナー
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Visualization of Ca2+ dynamics within the endoplasmic reticulum for the study of astrocytic functions2018

    • Author(s)
      Yohei Okubo, Kazunori Kanemaru, Masamitsu Iino
    • Organizer
      The 18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アストロサイトにおけるIP3受容体2型非依存性Ca2+放出2018

    • Author(s)
      大久保 洋平、金丸 和典、廣瀬 謙造、飯野 正光
    • Organizer
      生理研研究会「シグナル動態の可視化と操作に基づく多階層機能解析の新展開」
    • Related Report
      2018 Annual Research Report
  • [Presentation] Visualization of metabotropic glutamate receptor signaling in neurons2018

    • Author(s)
      Yohei Okubo
    • Organizer
      次世代薬理学セミナー2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] アストロサイト機能の解析に向けた小胞体内腔Ca2+動態可視化2017

    • Author(s)
      大久保 洋平、金丸 和典、飯野 正光
    • 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] Nitric oxide contributes to epileptic seizure-induced neuronal death2017

    • Author(s)
      Yohei Okubo
    • Organizer
      38th world congress of the international union of physiological sciences
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] てんかん誘発性神経細胞死を担う一酸化窒素依存性1型リアノジン受容体活性化2017

    • Author(s)
      大久保 洋平、三上 義礼、金丸 和典、飯野 正光
    • Organizer
      生理研研究会「シグナル動態の可視化と操作に基づく多階層機能解析の新展開」
    • Related Report
      2017 Research-status Report
  • [Presentation] Visualization of Ca2+ filling mechanisms upon synaptic inputs in the endoplasmic reticulum of cerebellar Purkinje cells2017

    • Author(s)
      Yohei Okubo, Junji Suzuki, Kazunori Kanemaru, Naotoshi Nakamura, Tatsuo Shibata, Masamitsu Iino
    • Organizer
      20th International Symposium on Calcium Binding Proteins and Calcium Function in Health and Disease
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 小胞体内腔Ca2+イメージングによる神経・グリア細胞機能の解析2017

    • Author(s)
      大久保 洋平
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 成熟マウス大脳皮質におけるmGluRを介した経験依存性シナプス維持機構2016

    • Author(s)
      大久保 洋平、久保田 淳、三上 義礼、金丸 和典、関谷 敬、飯野 正光
    • Organizer
      生理研研究会「生体シグナルダイナミクス研究会」
    • Place of Presentation
      生理学研究所(愛知県岡崎市)
    • Year and Date
      2016-09-15
    • Related Report
      2016 Research-status Report
  • [Presentation] 成熟マウス大脳皮質におけるmGluRを介した経験依存性シナプス維持機構2016

    • Author(s)
      大久保 洋平、久保田 淳、三上 義礼、金丸 和典、関谷 敬、飯野 正光
    • Organizer
      第134回 日本薬理学会関東部会
    • Place of Presentation
      国際医療福祉大学(栃木県大田原市)
    • Year and Date
      2016-07-06
    • Related Report
      2016 Research-status Report
  • [Remarks] 東京大学大学院医学系研究科細胞分子薬理学教室

    • URL

      http://calcium.cmp.m.u-tokyo.ac.jp/

    • Related Report
      2017 Research-status Report
  • [Remarks] 東京大学大学院医学系研究 科細胞分子薬理学教室

    • URL

      http://calcium.cmp.m.u-tokyo.ac.jp/

    • Related Report
      2016 Research-status Report

URL: 

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

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