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Molecula and neral mechanisms of individual- and -sex differences in behavioral resposne to stress

Research Project

Project/Area Number 18H02750
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 52030:Psychiatry-related
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) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsストレス / うつ病 / エピゲノム / エピジェネティクス / 個体差 / 性差 / ストレス脆弱性
Outline of Final Research Achievements

This study aimed to clarify the molecular mechanism of individual difference in stress adaptation. To this end, we performed a comprehensive gene expression analysis with stress-susceptible and -resilient mice and in clinical depression. We found increased KDM5C expression in depressed individual and stress-susceptible mice. We generated transgenic mice overexpressing KDM5C and found that these TgM has stress-vulnerability. Conversely, KDM5C knockout mice showed stress resilient phenotypes. We also identified two genes as KDM5C target genes, which are also involved in behavioral response to stress. These data suggest that KDM5C-mediated epigenetic gene expression could be involved in behavioral response to stress.

Academic Significance and Societal Importance of the Research Achievements

ストレスによる脳機能低下の個体差構築のメカニズム解明は、うつ病などのストレス性精神疾患の予防・治療法の確立につながることが期待される。本研究は、うつ病発症に関わるとされるストレス脆弱性の個体差構築にはエピジェネティックな遺伝子発現制御異常に起因する神経ネットワーク変容が関わるとの仮説を検証することを目的とした。その成果として、KDM5Cを介したエピジェネティックな遺伝子発現がストレス反応の個体差・性差構築に関わっていることが示唆され、KDM5Cを標的とした薬剤の抗ストレス・抗うつ作用が期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (12 results)

All 2021 2020 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 6 results)

  • [Journal Article] Distinct epigenetic signatures between adult-onset and late-onset depression.2021

    • Author(s)
      Yamagata H, Ogihara H, Matsuo K, Uchida S, Kobayashi A, Seki T, Kobayashi M, Harada K, Chen C, Miyata S, Fukuda M, Mikuni M, Hamamoto Y, Watanabe Y, Nakagawa S
    • Journal Title

      Sci Rep

      Volume: 27 Issue: 1 Pages: 2296-2296

    • DOI

      10.1038/s41598-021-81758-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of the signature of peripheral innate immunity in women with later-life major depressive disorder2021

    • Author(s)
      Miyata S, Yamagata H, Matsuo K, Uchida S, Harada K, Fujihara K, Yanagawa Y, Watanabe Y, Mikuni M, Nakagawa S, Fukuda M
    • Journal Title

      Brain Behav Immun

      Volume: 87 Pages: 831-839

    • DOI

      10.1016/j.bbi.2020.03.018

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AlteredexpressionoflongnoncodingRNAsinpatientswithmajordepressivedisorder2019

    • Author(s)
      Seki T, Yamagata H, Uchida S, Chen C, Kobayashi A, Kobayashi M, Harada K, Matsuo K, Watanabe Y, Nakagawa S.
    • Journal Title

      JournalofPsychiatricResearch

      Volume: 117 Pages: 92-99

    • DOI

      10.1016/j.jpsychires.2019.07.004

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] エピジェネティクスの視点から紐解く脳内ストレス適応の分子メカニズム2021

    • Author(s)
      内田周作
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 遺伝・環境相互作用によるレジリエンス形成の分子基盤2020

    • Author(s)
      内田周作
    • Organizer
      第50回日本神経精神薬理学会・第42回日本生物学的精神医学会・ 第4回日本精神薬学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Molecular and neural mechanisms of stress susceptibility and resilience2019

    • Author(s)
      内田周作
    • Organizer
      Neuro2019
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ストレスに強い脳と弱い脳の分子メカニズム2019

    • Author(s)
      内田周作
    • Organizer
      日本精神神経学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Epigenetic mechanisms of stress-induced depression2019

    • Author(s)
      内田周作
    • Organizer
      6th Congress of AsCNP
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Epigenetic mechanisms of stress susceptibility and resilience2019

    • Author(s)
      内田周作
    • Organizer
      American College of Neuropsychopharmacology
    • Related Report
      2019 Annual Research Report
  • [Presentation] ストレス関連精神疾患におけるカルシウムシグナリングの役割2018

    • Author(s)
      内田周作
    • Organizer
      第40回日本生物学的精神医学会・第61回日本神経化学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 運動によるストレスレジリエンス獲得の分子メカニズム2018

    • Author(s)
      内田周作
    • Organizer
      第73回日本体力医学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ストレス関連精神疾患におけるエピジェネティクス制御機構の破綻と神経可塑性異常2018

    • Author(s)
      内田周作
    • Organizer
      第59回日本組織細胞化学会
    • Related Report
      2018 Annual Research Report
    • Invited

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Published: 2018-04-23   Modified: 2022-01-27  

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