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Investigation of pathogenic mechanisms and Kampo medicine-based preventive and therapeutic strategy for ADHD using an epigenetic animal model.

Research Project

Project/Area Number 15K15269
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General internal medicine(including psychosomatic medicine)
Research InstitutionUniversity of Toyama

Principal Investigator

MATSUMOTO KINZO  富山大学, 和漢医薬学総合研究所, 教授 (10114654)

Co-Investigator(Kenkyū-buntansha) Suresh Awale  富山大学, 和漢医薬学総合研究所, 准教授 (00377243)
藤原 博典  富山大学, 和漢医薬学総合研究所, 助教 (10396442)
堀 悦郎  富山大学, 大学院医学薬学研究部(医学), 教授 (90313600)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords隔離飼育 / エピジェネティックモデル / 注意欠陥多動性障害 / 自閉症スペクトラム障害 / 発達障害 / 漢方薬 / 神経ステロイド / social isolation / ADHD model / developmental disorders / epigenetics / Kampo medicine / sociability / repeated behavior / Social isolation / attention-like behavior / 社会的隔離ストレス / エピジェネティックス / 発達障害モデル / ADHD / 行動異常 / 社会性行動
Outline of Final Research Achievements

We investigated pathogenic mechanisms of ADHD-related developmental disorder (DD) and effects of yokukansan (YKS) and keishito (KST), which are used for neuropsychiatric symptoms and cold of kids, respectively, on the disorders using socially isolated (SI) mice as an epigenetic model. SI-induced attention deficit was improved by YKS but not KST. However, when administrations of YKS and KST were started from early stage of SI, YKS and KST attenuated SI-induced DD-like behaviors. The effects of YKS and KST were due to improvement of neurosignaling systems in the hippocampus, suggesting that the administration of YKS and KST in early stage of development are beneficial for ADHD-related DD. Based on the finding that SI reduces the brain allopregnanolone (ALLO) contents, the effects of SKF105111, an ALLO biosynthesis inhibitor, on behavior was examined. The decrease of ALLO content by SKF105111 induced sociability deficit. Thus, it is likely that the decrease of ALLO is implicated in DD.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (21 results)

All 2018 2017 2016 2015

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (16 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Journal Article] Decrease in endogenous brain allopregnanolone induces autism spectrum disorder (ASD)-like behavior in mice: A novel animal model of ASD2017

    • Author(s)
      Ken Ebihara, Hironori Fujiwara, Suresh Awale, Dya Fita Dibwe, Ryota Arakai, Takeshi Yabe, Kinzo Matsumoto
    • Journal Title

      Behav. Brain Res.

      Volume: 334 Pages: 6-15

    • DOI

      10.1016/j.bbr.2017.07.019

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sansoninto, a traditional herbal medicine, ameliorates behavioral abnormalities and down-regulation of early growth response-1 expression in mice exposed to social isolation stress2017

    • Author(s)
      Fujiwara H., Tsushima R., Okada R., Awale S., Araki R., Yabe T., Matsumoto K.
    • Journal Title

      J Traditional and Complementary Medicine

      Volume: 印刷中 Issue: 1 Pages: 81-88

    • DOI

      10.1016/j.jtcme.2017.03.004

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Daily administration of yokukansan and keishito prevents social isolation-induced behavioral abnormalities and down-regulation of phosphorylation of neuroplasticity-related signaling molecules in mice2017

    • Author(s)
      Fujiwara H., Yaoyu, H., Ebihara K., Awale S., Araki R., Yabe T., Matsumoto K.
    • Journal Title

      BMC Complement Altern Med

      Volume: 17 Issue: 1 Pages: 195-195

    • DOI

      10.1186/s12906-017-1710-7

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Epigenetic regulation of dorsal raphe GABAB1a associated with isolation-induced abnormal behaviors in mice2015

    • Author(s)
      Araki R., Hiraki Y., Nishida S., Kuramoto N., Matsumoto K., Yabe T.
    • Journal Title

      Neuropharmacology

      Volume: 101 Pages: 1-12

    • DOI

      10.1016/j.neuropharm.2015.09.013

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] DNA methylation of the GC box in the promoter region suppresses transcription of srd5a1 in the prefrontal cortex2015

    • Author(s)
      Araki R., Nishida S., Hiraki Y., Matsumoto K., Yabe T.
    • Journal Title

      Neurosci. Lett.

      Volume: 606 Pages: 135-139

    • DOI

      10.1016/j.neulet.2015.08.031

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 発達障害の予防治療を志向した漢方薬のリポジショニング2018

    • Author(s)
      藤原博典,荒木良太,矢部武士,松本欣三
    • Organizer
      日本薬学会第138年会シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Repositioning of natural medicine for the preventive therapy of mild developmental disorders2017

    • Author(s)
      Fujiwara H. and Matsumoto K.
    • Organizer
      第90回日本薬理学会年会(シンポジウム)
    • Place of Presentation
      長崎ブッリクホール
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Sex difference in autism spectrum disorder (ASD)-like behaviors caused by allopregnanolone (ALLO) biosynthesis inhibition and distribution of ALLO in the brain2017

    • Author(s)
      Ebihara K.,Fujiwara H.,dya Fita Dibwe, Awale S., Araki R.,Yabe T.,Matsumoto K.
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブッリクホール
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
  • [Presentation] SKF105111 induced autism spectrum disorder (ASD) -like behavior may offer anovel animal model to explore therapeutic drugs for ASD2017

    • Author(s)
      1.Ken Ebihara, Hironori Fujiwara, Suresh Awale, Dya Fita Dibwe, Ryota Araki, Takeshi Yabe, Kinzo Matsumoto
    • Organizer
      The 1st International Conference on Natural Medicines: ICNM2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経ステロイドallopregnanoloneの生合成阻害による社会性行動低下に対する加味逍遥散の改善効果2017

    • Author(s)
      2.郭青雲,藤原博典,海老原健,Awale Suresh,荒木良太,矢部武士,松本欣三
    • Organizer
      第34回和漢医薬学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 自閉症スペクトラム(ASD)様症状発現における脳内神経ステロイド・アロプレグナノロンの役割と加味逍遥散による発現抑制2017

    • Author(s)
      3.松本欣三,郭青雲,海老原健,Awale Suresh,荒木良太,矢部武士,藤原博典
    • Organizer
      第16回日本臨床中医薬学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] マウスから学ぶ”こころと記憶の病”と和漢薬2017

    • Author(s)
      松本欣三
    • Organizer
      第60回富山県理科教育研究発表会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Experimental approach to developmental disorder treatment from traditional medicine2017

    • Author(s)
      松本欣三
    • Organizer
      日中友好病院中薬国際伝統医薬シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 隔離飼育マウスの発達障害様行動に及ぼす抑肝散及び桂枝湯の効果2016

    • Author(s)
      松本欣三, 藤原博典,韓ヨウウ,Awale Suresh, 荒木良太,矢部武士
    • Organizer
      第15回日本臨床中医薬学会学術大会
    • Place of Presentation
      京都府立医科大学
    • Year and Date
      2016-10-08
    • Related Report
      2016 Research-status Report
  • [Presentation] 神経ステロイドallopregnanoloneの生合成阻害による社会性行動の低下2016

    • Author(s)
      海老原健,藤原博典,荒木良太,矢部武,Suresh Awale, 松本欣三
    • Organizer
      第67回日本薬理学会北部会
    • Place of Presentation
      北海道大学
    • Year and Date
      2016-09-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Daily administration of keishito prevents social isolation-induced impairments of sociability and attention-related behaviors in mice2016

    • Author(s)
      藤原博典,韓 垚羽,岡田亮,スレスアワレ,荒木良太,矢部武士,松本欣三
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜国際会議場,横浜
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
  • [Presentation] Social isolation rearing of mice, a putative animal model of ADHD, and Kampo medicine2015

    • Author(s)
      松本欣三, 韓 垚羽, 岡田亮, 津島遼平, 藤原博典, Awale Suresh, 荒木良太, 矢部武士
    • Organizer
      第14回日本臨床中医薬学会学術大会
    • Place of Presentation
      パレブラン高志会館、富山
    • Year and Date
      2015-09-29
    • Related Report
      2015 Research-status Report
  • [Presentation] 発育環境に起因する異常行動と背側縫線核GABAB1aのエピジェネティクス制御の関連性2015

    • Author(s)
      荒木 良太,平城 陽介,西田 将治,酒井 樹生,太田 圭祐,細木 美沙,倉本 展行,松本 欣三,矢部 武士
    • Organizer
      第45回神経精神薬理学会
    • Place of Presentation
      タワーホール船堀,東京
    • Year and Date
      2015-09-24
    • Related Report
      2015 Research-status Report
  • [Presentation] 隔離飼育マウスにおけるADHD様行動の発現とそれに対する漢方薬・抑肝散の効果の検討2015

    • Author(s)
      韓 垚羽,藤原博典,岡田亮,Awale Suresh, 荒木良太,矢部武士,松本欣三
    • Organizer
      生体機能と創薬シンポジウム2015
    • Place of Presentation
      日本大学薬学部, 千葉
    • Year and Date
      2015-08-27
    • Related Report
      2015 Research-status Report
  • [Presentation] AD/HD様動物モデルでの病態発症機構と漢方薬作用:隔離飼育マウスでの検討2015

    • Author(s)
      松本欣三,藤原博典,韓 垚羽,Awale Suresh, 荒木良太,矢部武士
    • Organizer
      第32回和漢医薬学会学術大会(シンポジウム「精神疾患の緩和・治療に向けた漢方医薬学的アプローチ」)
    • Place of Presentation
      富山国際会議場,富山
    • Year and Date
      2015-08-22
    • Related Report
      2015 Research-status Report
  • [Presentation] 隔離飼育マウスのAD/HD様行動障害に対する抑肝散および甘麦大棗湯の改善効果の検討2015

    • Author(s)
      韓 垚羽,藤原博典,岡田亮,荒木良太,矢部武士,松本欣三
    • Organizer
      第32回和漢医薬学会学術大会
    • Place of Presentation
      富山国際会議場,富山
    • Year and Date
      2015-08-22
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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