• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Pharmacogenetics study for the treatment of early life stress induced fibromyalgia

Research Project

Project/Area Number 17H06978
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Orthodontics/Pediatric dentistry
Research InstitutionKagoshima University

Principal Investigator

Furukawa Minami  鹿児島大学, 医歯学域附属病院, 助教 (00806474)

Project Period (FY) 2017-08-25 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords幼少期ストレス / GABAスイッチ / KCC2 / NKCC1 / シナプス / 筋異常疼痛 / 薬理遺伝学
Outline of Final Research Achievements

In recent years, it is reported early life stress is involved in the onset of psychiatric disorders, developmental disorders, muscle pain. However, the cause is unknown. We examined whether neonatal stress can affect the timing of the GABA functional switch and cause disorders during adolescence. Neonatal stress was induced in C57BL/6J male mouse pups by maternal separation on postnatal days (PND) 1-21. We showed that maternal separation delayed the timing of the GABA switch in the hippocampus and inhibited the increase in membrane KCC2 expression, with KCC2 expression inhibition persisting until adolescence. Behavioral tests showed impaired cognition, declined attention, hyperlocomotion, and aggressive character in maternally separated mice. Taken together, our results show that neonatal stress delayed the timing of the GABA switch, which could change the E/I balance and cause neurodegenerative disorders in later life.

Academic Significance and Societal Importance of the Research Achievements

幼少期ストレスが、精神疾患や発達性障害、筋異常疼痛などの発症に関与することが報告されている。我々は幼少期ストレスにより、GABAスイッチが遅れ、細胞体周囲のKCC2の発現が減少し、NKCC1はほとんど影響を受けないことを初めて報告した。これにより、KCC2やGABAスイッチを介した、精神疾患や発達性障害、筋異常疼痛などの発症の予防、改善に抑制系の成熟を標的とした新たな治療法の確立が期待される。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • Research Products

    (10 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] ストレスに起因するGABA応答障害の動物実験的検証2019

    • Author(s)
      五十嵐 健人、富田 和男、桑原 義和、山西 沙祐里、古川 みなみ、宮脇 正一、栗政 明弘、佐藤 友昭
    • Journal Title

      東北医科薬科大学雑誌

      Volume: 65

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Delay of GABA switch due to early-life stress leads to developmental disorder.2018

    • Author(s)
      Furukawa M, Yamanishi S, Igarashi K, Tomita K, Miyawaki S, Sato T.
    • Journal Title

      Atlas of science.

      Volume: ー

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Neonatal maternal separation delays the GABA excitatory-to-inhibitory functional switch by inhibiting KCC2 expression2017

    • Author(s)
      Furukawa Minami、Tsukahara Takao、Tomita Kazuo、Iwai Haruki、Sonomura Takahiro、Miyawaki Shouichi、Sato Tomoaki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 493 Issue: 3 Pages: 1243-1249

    • DOI

      10.1016/j.bbrc.2017.09.143

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Neonatal maternal separation delays the GABA excitatory-to-inhibitory functional switch by inhibiting KCC2 expression and induces developmental disorders-like behaviors in mice.2018

    • Author(s)
      Furukawa M, Tsukahara T, Yamanishi S, Tomita K, Takashi Y, Tanaka K, Kitanaka J, Kitanaka N, Takemura M, Nishiyama N, Nishitani Y, Miyawaki S, Sato T.
    • Organizer
      WCP2018-18th world congress of basic and clinical pharmacology.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 覚醒時のストレス負荷と食道内酸刺激が咬筋活動に及ぼす影響.2018

    • Author(s)
      福嶋美佳,前田綾,大牟禮治人,迫口陽子,大賀泰彦,古川みなみ,大石章仁,大迫佑季,高橋広太郎,成昌建,宮脇正一.
    • Organizer
      第77回日本矯正歯科学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 片側性唇顎口蓋裂を伴う患者における上顎中切歯の歯根吸収と水平的な歯の移動および移植骨との関連.2018

    • Author(s)
      前田 綾, 古川 みなみ, 權 相豪, 丸谷 佳菜子, 中川 祥子, 渡邉 温子, 岐部 俊郎, 手塚 征宏, 渕上 貴央, 中村 典史, 宮脇 正一.
    • Organizer
      第42回日本口蓋裂学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 母子分離ストレスは雄性マウスにおいてGABAスイッチの時期を遅らせ,発達性障害様行動異常を誘発する2017

    • Author(s)
      古川 みなみ,塚原 飛央,富田 和男,高 裕子,宮脇 正一,佐藤 友昭
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ストレスによるGPR30過剰発現はAkt-WINK1の過敏反応を惹起し,KCC2を不活性化させることで,GABA抑制機能を低下させる2017

    • Author(s)
      塚原 飛央,古川 みなみ,富田 和男,岩井 治樹,高 裕子,薗村 貴弘,佐藤 友昭
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 母子分離雄性マウスに対するGABAスイッチを介した高次機能への影響2017

    • Author(s)
      古川 みなみ,塚原 飛央,富田 和男,高 裕子,田中 康一,北中 純一,北中 順恵,西谷 佳浩,竹村 基彦,西山 信好,宮脇 正一,佐藤 友昭
    • Organizer
      第70回日本薬理学会西南部会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 幼少期ストレスと発達性障害との関係解明-矯正治療の効率化に向けた検討-2017

    • Author(s)
      古川 みなみ,塚原 飛央,宮脇 正一,佐藤 友昭
    • Organizer
      第76回日本矯正歯科学会学術大会
    • Related Report
      2017 Annual Research Report

URL: 

Published: 2017-08-25   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi