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New behavioral animal model to study genetic and environmental factors in the cause of depression

Research Project

Project/Area Number 16K07100
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory animal science
Research InstitutionHyogo University of Health Sciences

Principal Investigator

DOE Nobutake  兵庫医療大学, 共通教育センター, 講師 (00434879)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsうつ病 / 動物モデル / 水迷路学習 / マウス / 行動的絶望 / 発症脆弱性 / 個体差 / エピジェネティクス / うつ動物モデル / 脆弱性 / 疾患モデル / 実験系心理学 / 行動学
Outline of Final Research Achievements

We have developed a new animal model of depression by modifying the water maze learning task in mice. When the difficulty of the task is increased by downsizing of the platform and removing external cues, some of the mice gradually abandon adaptive learning and become immobile; this response indicates a depression-like states. In this research, DNA microarray analysis of hippocampus was performed to investigate the genes contributing to depression-like phenotypes of the helpless mice. The analysis followed by validation using real-time PCR revealed significant alteration in the expression of several genes, including downregulation of Ttr (transthyretin). Thus, it is possible that the decrease in Ttr expression in the hippocampus may be involved in the induction of depressant-like states in mice.

Academic Significance and Societal Importance of the Research Achievements

本研究で扱ったうつ動物モデルは、遺伝的相同性が極めて高い近交系マウスを被験体としながら、うつ的状態に陥る個体と健常性を維持する個体を並行して得ることができる実験系である。今回、うつ的状態に陥った個体の海馬において発現低下が認められたTtr(トランスサイレチン)は、エピジェネティックなメカニズムの制御を受けて抗うつ効果の発現に関わっていると推測される遺伝子である。つまり、マウスのうつ的状態の誘発には、Ttr等の遺伝子のエピジェネティックなメカニズムを介した変化が関わっている可能性が示唆された。

Report

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

    (12 results)

All 2019 2018 2017 2016

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (6 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Intravenous administration of human adipose-derived stem cells ameliorates motor and cognitive function for intracerebral hemorrhage mouse model2019

    • Author(s)
      Kuramoto Yoji, Takagi Toshinori, Tatebayashi Kotaro, Beppu Mikiya, Doe Nobutaka, Fujita Mitsugu, & Yoshimura Shinichi
    • Journal Title

      Brain Research

      Volume: 1711 Pages: 58-67

    • DOI

      10.1016/j.brainres.2018.12.042

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adipose-derived stem cell therapy inhibits the deterioration of cerebral infarction by altering macrophage kinetics2019

    • Author(s)
      Tatebayashi Kotaro, Takagi Toshinori, Fujita Mitsugu, Doe Nobutaka, Nakagomi Takayuki, Matsuyama Tomohiro, & Yoshimura Shinichi
    • Journal Title

      Brain Research

      Volume: 1712 Pages: 139-150

    • DOI

      10.1016/j.brainres.2019.01.037

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-18-deficient mice develop hippocampal abnormalities related to possible depressive-like behaviors2019

    • Author(s)
      Yamanishi Kyosuke, Doe Nobutaka, Mukai Keiichiro, Ikubo Kaoru, Hashimoto Takuya, Uwa Noriko, Sumida Miho, El-Darawish Yosif, Gamachi Naomi, Li Wen, Kuwahara-Otani Sachi, Maeda Seishi, Watanabe Yuko, Hayakawa Tetsu, Yamanishi Hiromichi, Matsuyama Tomohiro, Yagi Hideshi, Okamura Haruki, & Matsunaga Hisato
    • Journal Title

      Neuroscience

      Volume: 408 Pages: 147-160

    • DOI

      10.1016/j.neuroscience.2019.04.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular analysis of the mouse brain exposed to chronic mild stress: The influence of hepatocyte nuclear factor 4α on physiological homeostasis2017

    • Author(s)
      Ikubo Kaoru、Yamanishi Kyosuke、Doe Nobutaka、Hashimoto Takuya、Sumida Miho、Watanabe Yuko、El-Darawish Yosif、Li Wen、Okamura Haruki、Yamanishi Hiromichi、Matsunaga Hisato
    • Journal Title

      Molecular Medicine Reports

      Volume: 16 Issue: 1 Pages: 301-309

    • DOI

      10.3892/mmr.2017.6577

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] マウスのモリス型水迷路学習課題における実験装置の条件設定の重要性2017

    • Author(s)
      土江伸誉
    • Journal Title

      行動科学

      Volume: 55 Pages: 1-11

    • NAID

      40021180529

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] CAPS1 RNA Editing Promotes Dense Core Vesicle Exocytosis.2016

    • Author(s)
      Miyake K, Ohta T, Nakayama H, Doe N, Terao Y, Oiki E, Nagatomo I, Yamashita Y, Abe T, Nishikura K, Kumanogoh A, Hashimoto K, Kawahara Y.
    • Journal Title

      Cell Reports

      Volume: 17 Issue: 8 Pages: 2004-2014

    • DOI

      10.1016/j.celrep.2016.10.073

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] インターロイキン18の欠損状態がうつ病など精神症状発現に及ぼす影響について~精神と免疫のクロストーク~2018

    • Author(s)
      山西恭輔、土江伸誉、橋本卓也、井窪薫、向井馨一郎、澄田美保、大谷(桑原)佐知、前田誠司、李 文、渡邊優子、宇和典子、早川 徹、山西博道、岡村春樹、松永寿人
    • Organizer
      第114回日本精神神経学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 複数の行動実験課題を併用したマウスのうつ的傾向の評価2018

    • Author(s)
      土江伸誉・高橋佑奈・長永夕奈
    • Organizer
      日本実験動物技術者協会関西支部平成29年度春季大会
    • Related Report
      2017 Research-status Report
  • [Presentation] IL-18 の欠損状態がうつ病など精神症状発現に及ぼす影響について -IL-18欠損マウスを用いた多角的検討-2017

    • Author(s)
      山西恭輔・松永寿人・土江伸誉・橋本卓也・井窪薫・澄田美保・大谷(桑原)佐知・前田誠司・李文・渡辺優子・宇和典子・早川徹・山西博道・岡村春樹
    • Organizer
      第113回日本精神神経学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Interleukin-18-deficient mice develop dysfunction of hippocampus resulting in depression-like behavior2017

    • Author(s)
      Yamanishi, K., Doe, N., Mukai, K., Ikubo, K., Hashimoto, T., Uwa, N., Sumida, M., Kuwahara-Otani, S., Maeda, S., Watanabe, Y., Li, W., Hayakawa, T., Okamura, H., Yamanishi, H., & Matsunaga, H.
    • Organizer
      WPA XVII World Congress of Psychiatry
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 水迷路学習場面で出現する行動的絶望マウスの血中サイトカイン濃度パターンの分析2016

    • Author(s)
      村山真人・笠原恵美子・澤野俊憲・山本英幸・桐山美香・土江伸誉・関山敦生
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県, 横浜市)
    • Year and Date
      2016-12-01
    • Related Report
      2016 Research-status Report
  • [Presentation] Interleukin-18-deficient mice develop dysfunction of hippocampus resulting in depression-like behavior2016

    • Author(s)
      Yamanishi, K., Doe, N., Ikubo, K., Sumida, M., Kuwahara-Otani, S., Maeda, S., Watanabe, Y., Yoshida, M., Li, W., Hayakawa, T., Okamura, H., Yamanishi, H., & Matsunaga, H.
    • Organizer
      30th CINP World Congress of Neuropsychopharmacology
    • Place of Presentation
      COEX(Seoul, KOREA)
    • Year and Date
      2016-07-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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