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Formation of emotional functions of next generation depending on paternal psychological stress

Research Project

Project/Area Number 20K16859
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionThe University of Tokushima

Principal Investigator

SHIMIZU Noriyuki  徳島大学, 大学院医歯薬学研究部(医学域), 助教 (70755470)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords心理的ストレス / 父親 / 次世代 / 情動機能 / グルココルチコイド / マウス / 情動行動 / 脳機能 / コルチコステロン
Outline of Research at the Start

日本での不安障害・うつ病をはじめとする精神疾患の患者数は年々増加しており、その防止策が社会的に求められている。本研究では、交配前までに父親マウスが受けた継続的なストレスが、エピジェネティクスな制御機構にもとづき、どのような作用機序を介して次世代仔マウスの脳機能に影響を及ぼすかを明らかとし、将来に起こりうる情動行動の異常に対する対処法を探索する。本研究成果より、父親が次世代の脳機能発達に果たす新たな役割と重要性を見出し、ヒトの精神疾患に対して治療ではなく予防の視点から貢献できる可能性を提示する。

Outline of Final Research Achievements

In this study, we investigated the mechanism of impairment of emotional behaviors (anxiety-like behavior, depression-like behavior, extreme avoidance behavior in response to aversive stimuli, and decreased social behavior) occur in offspring from paternal mice that have continuously subjected psychological stress. We found that administration of a glucocorticoid receptor antagonist (RU-486) to paternal mice during the period of psychological stress can avoid the abnormality of emotional behaviors in next-generation offspring. On the other hand, we found that continuous administration of a glucocorticoid receptor agonist (dexamethasone) to paternal mice cause the change of emotional behaviors like next-generation offspring caused by psychological stress. These suggest that next-generation construction of emotional function may be influenced by the paternal glucocorticoid system.

Academic Significance and Societal Importance of the Research Achievements

不安障害・うつ病をはじめとする精神疾患の患者数は増加しており、予防策の構築が求められている。精神疾患は、遺伝的背景や環境因子が複雑に関連しており、その作用機序は未だ明らかではない。本研究では、父親が受ける継続的なストレスが、エピジェネティクスな制御機構に基づき、どのような作用機序を介して次世代の情動機能に影響を及ぼすかを明らかとする。本研究成果は、父親が次世代の情動機能構築に果たす新たな役割と重要性を見出せるものであり、ヒトの精神疾患に対して予防の視点から貢献できる可能性を提示できるものと考えられる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (7 results)

All 2023 2022 2021

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (3 results)

  • [Journal Article] Dual orexin receptor antagonist drug suvorexant can help in amelioration of predictable chronic mild stress-induced hyperalgesia2022

    • Author(s)
      Chavan Parimal、Chikahisa Sachiko、Shiuchi Tetsuya、Shimizu Noriyuki、Dalanon Junhel、Okura Kazuo、Sei Hiroyoshi、Matsuka Yoshizo
    • Journal Title

      Brain Research Bulletin

      Volume: 188 Pages: 39-46

    • DOI

      10.1016/j.brainresbull.2022.07.011

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Feeding Rhythm-Induced Hypothalamic Agouti-Related Protein Elevation via Glucocorticoids Leads to Insulin Resistance in Skeletal Muscle2021

    • Author(s)
      Shiuchi T, Otsuka A, Shimizu N, Chikahisa S, Sei H.
    • Journal Title

      Int J Mol Sci.

      Volume: 22 Issue: 19 Pages: 10831-10831

    • DOI

      10.3390/ijms221910831

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pain sensitivity increases with sleep disturbance under predictable chronic mild stress in mice2021

    • Author(s)
      Dalanon J, Chikahisa S, Shiuchi T, Shimizu N, Chavan P, Suzuki Y, Okura K, Sei H, Matsuka Y
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41598-021-93560-7

    • NAID

      120007125049

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intracranial mast cells contribute to the control of social behavior in male mice2021

    • Author(s)
      Tanioka Daisuke、Chikahisa Sachiko、Shimizu Noriyuki、Shiuchi Tetsuya、Sakai Noriaki、Nishino Seiji、Sei Hiroyoshi
    • Journal Title

      Behavioural Brain Research

      Volume: 403 Pages: 113143-113143

    • DOI

      10.1016/j.bbr.2021.113143

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Exercise training of paternal mice subjected to continuous psychological stress prior to mating may modify changes in their offspring’s emotional behaviors2023

    • Author(s)
      Shimizu Noriyuki, Chikahisa Sachiko, Shiuchi Tetsuya, Sei Hiroyoshi
    • Organizer
      日本生理学会 第100回記念大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Paternal exposure to psychological stress before mating may influence a formation of emotional behavior in next generation via effect of glucocorticoid2022

    • Author(s)
      Shimizu Noriyuki, Chikahisa Sachiko, Shiuchi Tetsuya, Sei Hiroyoshi
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 交配前に心理的ストレスを受けた父親マウスに由来する次世代仔マウスの情動行動変化はグルココルチコイド受容体拮抗薬で防ぐことができる2022

    • Author(s)
      Shimizu Noriyuki, Chikahisa Sachiko, Shiuchi Tetsuya, Sei Hiroyoshi
    • Organizer
      NEURO2022
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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