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Pathophysiological analysis of mental disorder caused by disturbance of GABAergic system in the brain due to maternal separation stress and search for treatment methods

Research Project

Project/Area Number 20K07270
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48020:Physiology-related
Research InstitutionHirosaki University

Principal Investigator

YAMADA JUNKO  弘前大学, 保健学研究科, 教授 (30334965)

Co-Investigator(Kenkyū-buntansha) 小枝 周平  弘前大学, 保健学研究科, 講師 (00455734)
冨山 誠彦  弘前大学, 医学研究科, 教授 (40311542)
佐藤 ちひろ  弘前大学, 保健学研究科, 助教 (70757468)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsストレス / 母子分離 / 雌雄差 / 社会的孤立 / 不安 / 記憶機能低下 / 母子分離マウス / ネグレクト / 運動介入 / 社会的ストレス / GABA / 脳 / 発達障害
Outline of Research at the Start

幼少期に生じたストレスは成長に伴いさまざまな疾患に罹患する確率が高く、成長後の脳機能や構造に重大な問題を引き起こすことが示唆されているが、その機序は未だ明らかではない。ストレス脆弱性の臨界期にGABAが興奮性に働き、細胞移動・シナプス形成・強化にかかわることに着目し、幼少期虐待モデル動物である母子分離マウスを用いて、ストレスによるGABA応答の変異に関し細胞、分子レベルでの解析を行い病態解明を行う。次に介入による脳機能への可塑的効果を解析し、ささらにはストレスを受けた子の次世代の養育行動への影響を解析することで、ストレスを受けたこどもへの根拠ある養育環境の改善のためのエビデンスを確立する。

Outline of Final Research Achievements

Stress caused by neglect in early childhood increases the probability of developing various disorders such as anxiety disorders, depression, and eating disorders. In this study, we used maternal separation mice as a model of neglect, and conducted behavioral, brain function, and stress assessments, as well as sex difference analyses, in order to investigate the causes of increased anxiety, addictive, and depressive behaviors that occur after the separation of mother and child, and to analyze the effects of intervention on recovery, and to analyze changes in the brain. The effects of mother-infant separation were strongly observed in male mice, including depression and stress-induced hyperactivity. Longer mother-infant separation time suppressed body weight gain in males, but not in females. Exercise intervention was found to be effective in improving depression-like behavior.

Academic Significance and Societal Importance of the Research Achievements

近年児童虐待が社会問題化してきており年々増加傾向にある。幼少期のストレスは成長後様々な精神的、身体的問題を引き起こす。特に精神的虐待及びネグレクトは重度の鬱病を引き起こすと言われている。本研究ではネグレクトモデルとして母子分離マウスを用いた研究を行った。母子分離による影響は雄マウスに強く表れ、不安様行動、体重増加の抑制などが顕著にみられた。自由に運動できる環境におかれた母子分離群では不安様行動は見られなかったことから運動介入が何らかのストレス改善効果に関わっていることがわかった。このことから、母子分離により成長後も行動への影響が残存するが、運動など介入をすることにより改善する可能性が示唆された

Report

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

    (15 results)

All 2023 2021 2020

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

  • [Journal Article] Effect of Ionizing Radiation on the Intercellular Network of Murine Cerebral Cortical Neurons2023

    • Author(s)
      Masaru Yamaguchi, Takakiyo Tsujiguchi, Tomonori Furukawa, Shuji Shimoyama, Toshiya Nakamura, Yasushi Mariya, Junko Yamada
    • Journal Title

      Radiation Environment and Medicine

      Volume: 12 Issue: 1 Pages: 65-73

    • DOI

      10.51083/radiatenvironmed.12.1_65

    • ISSN
      2423-9097, 2432-163X
    • Year and Date
      2023-02-27
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Trajectories of emotional and behavioral problems in school-age children with coordination difficulties and their relationships to ASD/ADHD traits2023

    • Author(s)
      Mikami Misaki、Hirota Tomoya、Adachi Masaki、Takahashi Michio、Nishimura Tomoko、Saito Manabu、Nakamura Kazuhiko、Yamada Junko
    • Journal Title

      Research in Developmental Disabilities

      Volume: 133 Pages: 104394-104394

    • DOI

      10.1016/j.ridd.2022.104394

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Atypical Sensory Processing Profiles and Their Associations With Motor Problems In Preschoolers With Developmental Coordination Disorder2020

    • Author(s)
      Mikami Misaki、Hirota Tomoya、Takahashi Michio、Adachi Masaki、Saito Manabu、Koeda Shuhei、Yoshida Kazutaka、Sakamoto Yui、Kato Sumi、Nakamura Kazuhiko、Yamada Junko
    • Journal Title

      Child Psychiatry & Human Development

      Volume: 52 Issue: 2 Pages: 311-320

    • DOI

      10.1007/s10578-020-01013-5

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 「脳可塑性は可能性 機能回復と脳回復  ~動物を用いた基礎研究から~」2021

    • Author(s)
      山田順子
    • Organizer
      第15回日本作業療法研究学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 自閉症モデルマウスに対する強制運動の悪影響2021

    • Author(s)
      小枝周平、柳町穂実、三上美咲、佐藤ちひろ、山田順子
    • Organizer
      第55回日本作業療法学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Enrich environment causes the emotional and behavioral changes to the mouse model of autism spectrum disorder2021

    • Author(s)
      Shuhei Koeda , Honami Yanagimachi , Misaki Mikami , Chihiro Sato , Junko Yamada
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 発達障碍児の間隔特異性と栄養素摂取との関係2021

    • Author(s)
      秋山郁菜絵、小枝周平、三上美咲、斉藤まなぶ、山田順子
    • Organizer
      第55回日本作業療法学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 5歳における発達性協調運動障害児の筋力2021

    • Author(s)
      三上美咲・斉藤まなぶ・小枝周平・大里絢子・増田貴人・中村和彦・山田順子
    • Organizer
      第4回本DCD学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 幼児期における発達障害児の筆記具操作と描線運動2020

    • Author(s)
      三上美咲, 小枝周平 , 斉藤まなぶ, 中村和彦, 山田順子
    • Organizer
      第54回日本作業療法学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 手指の静的触覚機能に皮膚硬度が与える影響2020

    • Author(s)
      小枝周平, 三上美咲, 斉藤まなぶ, 中村和彦, 山田順子
    • Organizer
      第54回日本作業療法学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 脳出血モデルラットにおける運動種類の違いが運動麻痺回復および脳可塑性関連因子に及ぼす影響2020

    • Author(s)
      佐藤ちひろ, 小枝周平, 三上美咲, 山田順子
    • Organizer
      第54回日本作業療法学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 脳出血ラットにおける運動種類の違いが機能回復に与える影響2020

    • Author(s)
      佐藤ちひろ, 小枝周平, 三上美咲, 山田順子
    • Organizer
      第52回東北生理談話会
    • Related Report
      2020 Research-status Report
  • [Presentation] The motor recovery synaptic plasticity after stroke were affected by the types of exercise2020

    • Author(s)
      Chihiro Sato, Kunikazu Tanji, Mitsuru Chiba, Shuhei Koeda, Misaki Mikami, Junko Yamada
    • Organizer
      The 43th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2020 Research-status Report
  • [Presentation] The motor recovery and synaptic plasticity was affected by the types of exercise in the hemorrhage model rat.2020

    • Author(s)
      Chihiro Sato, Kunikazu Tanji, Koeda Shuhei, Mana Kishimoto, Shun Mori, Misaki Mikami, Junko Yamada
    • Organizer
      the 98th Annual Meeting of The Physiological Society of Japan, the 126th Annual Meeting of The Japanese Association of Anatomists
    • Related Report
      2020 Research-status Report
  • [Presentation] Sensory processing abnormalities and their associations with behavioral and emotional difficulties in preschoolers with Developmental Coordination Disorder.2020

    • Author(s)
      Misaki Mikami, Masaki Adachi, Michio Takahashi, Tomoya Hirota, Manabu Saito, Shuhei Koeda, Kazutaka Yoshida, Kazuhiko Nakamura, Junko Yamada
    • Organizer
      The International Association for Child and Adolescent Psychiatry and Allied Professions' (IACAPAP) 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research

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

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