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Molecular basis of emotional behavior abnormalities induced by juvenile stress

Research Project

Project/Area Number 16K10182
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Psychiatric science
Research InstitutionHiroshima University (2019)
Hokkaido University (2016-2018)

Principal Investigator

Yoshida Takayuki  広島大学, 医系科学研究科(医), 准教授 (60374229)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords幼若期ストレス / うつ様行動 / シナプス伝達 / 活動電位 / ケタミン / 内側前頭前皮質 / セロトニン / オキシトシン / 情動機能 / 神経活動 / 扁桃体
Outline of Final Research Achievements

Using rodents, we investigated novel molecular, neural circuitry, and behavioral mechanisms related to postmaturity anxiety disorders or depressive like behavior caused by juvenile stress. The juvenile stress was associated with a decrease in instinctive elevated/novel environmental anxiety levels, an excess of fear memory extinction, a decrease in social anxiety levels, and an increase in depressive like behavior. In the amygdala of these juvenile stressed animals, an increased frequency of neuronal action potentials and low sensitivity to serotonin were observed. We also found that ketamine treatment improved depressive behavior, which was related to the restoration of the balance between excitatory and inhibitory synaptic inputs in the medial prefrontal cortex.

Academic Significance and Societal Importance of the Research Achievements

不安障害や気分障害は脳内のセロトニンなどのモノアミン系神経伝達物質の低下が原因とする仮説が提唱されているが、本研究では、セロトニン作動性神経調節に加え、グルタミン酸作動性調節が情動機能調節に重要であり、その責任脳部位として扁桃体ならびに内側前頭前皮質における神経伝達修飾メカニズムが関与していることを電気生理学的、神経化学的ならびに行動学的に明らかにした。これは思春/青年期のストレス障害の発症機序ならびに神経精神基盤の成熟に与える影響について新規の分子・神経回路・行動メカニズムとして重要な知見であると考えられる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (13 results)

All 2020 2019 2017 2016 Other

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

  • [Int'l Joint Research] 国立衛生研究所(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] NIH/NIAAA(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] 国立衛生研究所(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Behavioral characteristics of 5-HT2C receptor knockout mice: Locomotor activity, anxiety-, and fear memory-related behaviors2020

    • Author(s)
      Nebuka Mao、Ohmura Yu、Izawa Shuntaro、Bouchekioua Youcef、Nishitani Naoya、Yoshida Takayuki、Yoshioka Mitsuhiro
    • Journal Title

      Behavioural Brain Research

      Volume: 379 Pages: 112394-112394

    • DOI

      10.1016/j.bbr.2019.112394

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] CRISPR/Cas9-mediated in vivo gene editing reveals that neuronal 5-HT1A receptors in the dorsal raphe nucleus contribute to body temperature regulation in mice2019

    • Author(s)
      Nishitani Naoya、Ohmura Yu、Nagayasu Kazuki、Shibui Norihiro、Kaneko Shuji、Ohashi Akiko、Yoshida Takayuki、Yamanaka Akihiro、Yoshioka Mitsuhiro
    • Journal Title

      Brain Research

      Volume: 1719 Pages: 243-252

    • DOI

      10.1016/j.brainres.2019.06.009

    • NAID

      120006885155

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blonanserin suppresses impulsive action in rats2019

    • Author(s)
      Nishitani Naoya、Sasamori Hitomi、Ohmura Yu、Yoshida Takayuki、Yoshioka Mitsuhiro
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 141 Issue: 3 Pages: 127-130

    • DOI

      10.1016/j.jphs.2019.09.013

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 扁桃体基底核錐体細胞に与える幼若期ストレスの影響2017

    • Author(s)
      小冷碧
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール、長崎新聞文化ホールアストピア(長崎県・長崎市)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
  • [Presentation] 幼若期ストレスによる成熟期の情動伝染の変容とマウス脳神経細胞の膜特性変化2017

    • Author(s)
      吉田隆行
    • Organizer
      第40回日本神経科学大会 幕張メッセ(千葉県・千葉市)
    • Related Report
      2017 Research-status Report
  • [Presentation] Juvenile stress-induced alteration of emotional contagion and intrinsic neuronal membrane plasticity in the mouse brain2017

    • Author(s)
      Takayuki Yoshida
    • Organizer
      Neuroscience 2017 ウォルターEワシントン国際会議場(ワシントンDC・USA)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 幼若期ストレスによって生じる扁桃体錐体細胞の膜興奮特性の変化2016

    • Author(s)
      吉田隆行
    • Organizer
      第39回日本神経科学学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Remarks] 北海道大学大学院医学研究院神経薬理学教室 研究内容

    • URL

      http://hokudaineuropharmacol.com/research/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 北海道大学大学院医学研究院神経薬理学教室 業績紹介

    • URL

      http://hokudaineuropharmacol.com/works/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 北海道大学大学院医学研究院薬理学分野神経薬理学教室

    • URL

      http://hokudaineuropharmacol.com

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2022-02-21  

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