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Molecular and neural mechanisms of stress resilience mediated by running exercise

Research Project

Project/Area Number 21K19707
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research InstitutionKyoto University

Principal Investigator

Uchida Shusaku  京都大学, 医学研究科, 特定准教授 (10403669)

Project Period (FY) 2021-07-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2021: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywordsストレス / うつ / レジリエンス / 運動 / うつ病 / エピジェネティクス / ヒストン脱アセチル化酵素 / 運動トレーニング
Outline of Research at the Start

心理・社会ストレスは、ストレス抵抗性・回復力や記憶・認知などの高次脳機能を低下させることで精神疾患の発症リスク増大につながると想定されている。一方、適度な運動が低中等度のうつ病患者に対して有効である可能性が示唆されている。しかし、運動トレーニングがストレスレジリエンスを獲得する脳内メカニズムはいまだに不明である。本研究課題では、運動によるストレスレジリエンス獲得の分子・神経メカニズムを解明する。得られた成果は、運動による健康維持・増進の理解につながるだけでなく、ストレス性精神疾患の予防法や治療法の開発に資する可能性が期待できる。

Outline of Final Research Achievements

Psychological and social stress is assumed to increase the risk of developing mental illnesses by impairing higher brain functions such as stress resistance, recovery, memory, and cognition. On the other hand, moderate exercise has been shown to activate the hippocampal region of the brain, which is important for memory formation, and exercise therapy has been suggested to be effective for patients with mild to moderate depression. However, the brain mechanisms by which exercise training acquires stress resilience are still unclear. In this research project, the applicant aims to clarify the molecular and neural mechanisms of stress resilience acquisition by exercise by focusing on epigenetic regulatory molecules that they have independently identified using their own highly valid depression model mice.

Academic Significance and Societal Importance of the Research Achievements

これまでの運動と脳機能との関連研究の最大の問題点は、”現象論の記述”に留まっていることであり、運動トレーニングがストレスレジリエンスを獲得する脳内メカニズムはいまだに不明であった。本研究では、この問題点を克服するために、申請者が独自に確立した妥当性の高いうつ病モデルマウスを用いて、独自に見出したエピジェネティクス制御分子に着目することで、運動トレーニングによるストレスレジリエンス獲得の分子・神経メカニズムの一端を明らかにした。得られた成果は、運動による健康維持・増進の理解につながるだけでなく、ストレス性精神疾患の予防法や治療法の開発に資する可能性が期待できる。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (12 results)

All 2023 2022 2021

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] GPCR-mediated calcium and cAMP signaling determines psychosocial stress susceptibility and resiliency2023

    • Author(s)
      Hiromichi Inaba, Haiyan Li, Ayako Kawatake-Kuno, Ken-ichi Dewa, Jun Nagai, Naoya Oishi, Toshiya Murai, and Shusaku Uchida
    • Journal Title

      Science Advances

      Volume: ー

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Experience-Regulated Neuronal Signaling in Maternal Behavior2022

    • Author(s)
      Fuentes Ileana、Morishita Yoshikazu、Gonzalez-Salinas Sofia、Champagne Frances A.、Uchida Shusaku、Shumyatsky Gleb P.
    • Journal Title

      Frontiers in Molecular Neuroscience

      Volume: 15

    • DOI

      10.3389/fnmol.2022.844295

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Editorial: The role of epigenetics in neuropsychiatric disorders2022

    • Author(s)
      Shirinian Margret、Chen Chong、Uchida Shusaku、Jadavji Nafisa M.
    • Journal Title

      Frontiers in Molecular Neuroscience

      Volume: 15

    • DOI

      10.3389/fnmol.2022.985023

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ストレス感受性制御の脳内分子基盤2022

    • Author(s)
      内田周作
    • Journal Title

      日本生物学的精神医学会誌

      Volume: 33 Pages: 22-25

    • Related Report
      2022 Annual Research Report
  • [Journal Article] 運動によるストレスレジリエンス獲得におけるエピジェネティック修飾2022

    • Author(s)
      内田周作
    • Journal Title

      体育の科学

      Volume: 72 Pages: 837-842

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Antidepressant Response and Stress Resilience Are Promoted by CART Peptides in GABAergic Neurons of the Anterior Cingulate Cortex2022

    • Author(s)
      Funayama Yuki、Li Haiyan、Ishimori Erina、Kawatake-Kuno Ayako、Inaba Hiromichi、Yamagata Hirotaka、Seki Tomoe、Nakagawa Shin、Watanabe Yoshifumi、Murai Toshiya、Oishi Naoya、Uchida Shusaku
    • Journal Title

      Biological Psychiatry Global Open Science

      Volume: ー Issue: 1 Pages: 87-98

    • DOI

      10.1016/j.bpsgos.2021.12.009

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Molecular Basis of Depression: Implications of Sex-Related Differences in Epigenetic Regulation2021

    • Author(s)
      Kawatake-Kuno Ayako、Murai Toshiya、Uchida Shusaku
    • Journal Title

      Frontiers in Molecular Neuroscience

      Volume: 14

    • DOI

      10.3389/fnmol.2021.708004

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Multiscale View of the Mechanisms Underlying Ketamine’s Antidepressant Effects: An Update on Neuronal Calcium Signaling2021

    • Author(s)
      Kawatake-Kuno Ayako、Murai Toshiya、Uchida Shusaku
    • Journal Title

      Frontiers in Behavioral Neuroscience

      Volume: 15

    • DOI

      10.3389/fnbeh.2021.749180

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Constructive understanding of the mechanisms underlying psychosocial stress-induced behavioral heterogeneity2023

    • Author(s)
      Shusaku Uchida
    • Organizer
      Molecular and Cellular Cognition Society Asia
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Epigenetic mechanisms driving synaptic plasticity and affective states under stressful situation2021

    • Author(s)
      Shusaku Uchida
    • Organizer
      日本神経科学会
    • Related Report
      2021 Research-status Report
  • [Presentation] ケタミン代謝産物による持続的な抗うつ作用の分子神経メカニズム2021

    • Author(s)
      Ayako Kawatake-Kuno, Erina Ishimori, Haiyan Li, Yusuke Sakai, Yuki Funayama, Hiromichi Inaba, Naoya Oishi, Toshiya Murai, Shusaku Uchida
    • Organizer
      日本神経化学会
    • Related Report
      2021 Research-status Report
  • [Presentation] ストレス感受性制御における脳内分子基盤2021

    • Author(s)
      内田周作
    • Organizer
      日本精神神経薬理学会
    • Related Report
      2021 Research-status Report

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Published: 2021-07-13   Modified: 2024-01-30  

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