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Molecular mechanisms of the enhancement of conditioned fear memory induced by maternal separation

Research Project

Project/Area Number 24791248
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Psychiatric science
Research InstitutionNational Defense Medical College

Principal Investigator

TODA Hiroyuki  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 医学教育部医学科専門課程, 助教 (00610677)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsニューロテンシン / 扁桃体 / 恐怖条件付けモデル / エピジェネティクス / 母子分離ストレス / エピジェネティック / 恐怖条件付け / 不安 / 恐怖記憶 / 消去 / 再固定
Research Abstract

Stress during postnatal development is associated with an increased risk for depression and anxiety disorders later in life. With respect to conditioned fear, previous studies have indicated that early life stress influences its development in adulthood. The results showed that maternal separation (MS) enhanced freezing behaviors in fear-conditioned stress and reduced the gene expression of neurotensin receptor (NTSR) 1 in the amygdalas of adult rats. The microinjection of a NTSR1 antagonist into the amygdala increased the percentage of freezing in conditioned fear. Moreover, MS increased DNA methylation in the promoter region of NTSR1 in the amygdala. MS may leave epigenetic marks in the NTSR1 gene in the amygdala, which may enhance conditioned fear in adulthood. The MS-induced alternations of DNA methylation in the promoter region of NTSR1 in the amygdala may be associated with vulnerability to the development of anxiety disorders and depression in adulthood.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (6 results)

All 2016 2014 2011 2010 2009

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (4 results)

  • [Journal Article] Maternal separation enhances conditioned fear and decreases the mRNA levels of the neurotensin receptor 1 gene with hypermethylation of this gene in the rat amygdala2016

    • Author(s)
      Hiroyuki Toda, Shuken Boku, Shin Nakagawa, Takeshi Inoue, Akiko Kato, Naoki Takamura, Ning Song, Masashi Nibuya, Tsukasa Koyama, Ichiro Kusumi
    • Journal Title

      PLOS ONE

      Volume: in press

    • NAID

      120005537461

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Maternal Separation Enhances Conditioned Fear and Decreases the mRNA Levels of the Neurotensin Receptor 1 Gene with Hypermethylation of This Gene in the Rat Amygdala2014

    • Author(s)
      Hiroyuki Toda, Shuken Boku, Shin Nakagawa, Takeshi Inoue, Akiko Kato, Naoki Takamura, Ning Song, Masashi Nibuya, Tsukasa Koyama, Ichiro Kusumi
    • Journal Title

      PLoS One

      Volume: 15

    • NAID

      120005537461

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] Vulnerability to anxiety behavior induced by maternal separation stress may occur through the increase of DNA methylation at neurotensin type 1 receptor promoter region in rat amygdala2011

    • Author(s)
      H Toda, S Nakagawa, S Boku, N Song, N Takamura, A Kato, T Inoue, T Koyama
    • Organizer
      Neuroscience 2011
    • Place of Presentation
      Washington DC
    • Related Report
      2013 Final Research Report
  • [Presentation] Maternal separation stress and vulnerability to anxiety behavior in rats2010

    • Author(s)
      H Toda, S Nakagawa, S Boku, Ning Song, N Takamura, A Kato, T Inoue, T Koyama
    • Organizer
      International College of Neuropsychopharmacology
    • Place of Presentation
      Houg Kong
    • Related Report
      2013 Final Research Report
  • [Presentation] Influence of early-life stress on behavior, HPA axis activity, gene expressions and hippocampal neurogenesis in adulthood rats2010

    • Author(s)
      H Toda, S Nakagawa, S Boku, N Takamura, N Song, A Kato, T Inoue, T Koyama
    • Organizer
      Neuroscience 2010
    • Place of Presentation
      San Diego
    • Related Report
      2013 Final Research Report
  • [Presentation] Dexamethasone/corticotrophin releasing hormone test in maternal separation stress models2009

    • Author(s)
      H Toda, S Nakagawa, S Boku, Ning Song, A Kato, T Inoue, T Koyama
    • Organizer
      Neuroscience 2009
    • Place of Presentation
      Cicago
    • Related Report
      2013 Final Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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