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Controlling mechanisms of the serotonergic system by a clock gene Rev-erb alpha relating to bipolar disorder

Research Project

Project/Area Number 16K19781
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Psychiatric science
Research InstitutionWakayama Medical University

Principal Investigator

Otsuka Tsuyoshi  和歌山県立医科大学, 医学部, 学内助教 (60760395)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords時計遺伝子 / Rev-erbα / セロトニン / 情動障害 / 前頭前皮質 / 双極性障害 / Rev-erb α / 脳
Outline of Final Research Achievements

Dysfunction of Rev-erbα, a core circadian clock gene, has been associated with Pathogenesis of affective disorder including bipolar disorder. However, detailed molecular mechanisms remain unclear. In this study, we found dysregulation of serotonergic system in Rev-erbα knockout mice. Despite a reduction in genes expression of key enzymes of serotonin synthesis, knockout mice show normal levels of serotonin and its metabolite in the dorsal raphe nuclei. However, prefrontal cortex, an important target of serotonin, shows the reduction of serotonin levels in knockout animals. These results indicate that serotonin release is impaired in Rev-erbα knockout mice. In addition, the expression of genes related to neuronal activity was decreased in the prefrontal cortex of Rev-erbα knockout mice. Therefore, we have concluded that defect in Rev-erbα may play an important role in organizing the serotonergic system in mammals.

Report

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

    (15 results)

All 2018 2017 2016

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (14 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Impact of heart-specific disruption of the circadian clock on systemic glucose metabolism in mice2017

    • Author(s)
      Nakao T, Kohsaka A, Otsuka T, Thein ZL, Le HT, Waki H, Gouraud SS, Ihara H, Nakanishi M, Sato F, Muragaki Y, Maeda M.
    • Journal Title

      Chronobiol Int

      Volume: in press Issue: 4 Pages: 499-510

    • DOI

      10.1080/07420528.2017.1415922

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Effect of Rev-erbα deficiency on the serotonergic system and mood regulation in mice2018

    • Author(s)
      Otsuka T, Kohsaka A, Le T H, Nakao T, Thein L Z, Maeda M
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Role of the circadian transcriptional repressor, REV-ERBα in the regulation of food intake under stress.2018

    • Author(s)
      Thein L Z, Kohsaka A, Otsuka T, Tsujimoto T, Le T H, Nakao T, Maeda M
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The Nuclear Receptor REV-ERBα Alters Mood and Neurotransmission in the Prefrontal Cortex.2017

    • Author(s)
      T. Otsuka, A. Kohsaka, H. T. Le, T. Nakao, Z. L. Thein, M. Maeda
    • Organizer
      Experimental Biology
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2017-04-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Transcriptome analysis reveals dysregulation of the prefrontal neuronal networks of Rev-erbα deficient mice.2017

    • Author(s)
      T. Otsuka, A. Kohsaka, H. T. Le, T. Nakao, Z. L. Thein, M. Maeda
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      アクトシティ浜松
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Circadian desynchronization alters mood and the regulation of genes associated with neuronal activity in the prefrontal cortex of mice.2017

    • Author(s)
      H. T. Le, T. Otsuka, A. Kohsaka, T. Nakao, Z. L. Thein, M. Maeda
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      アクトシティ浜松
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Alteration in mood and serotonergic pathways in Rev-erbα deficient mice2017

    • Author(s)
      Otsuka T, Kohsaka A, Le T H, Nakao T, Thein L Z, Maeda M
    • Organizer
      Consortium of Biological Sciences
    • Related Report
      2017 Annual Research Report
  • [Presentation] ストレス下の摂食調節における時計遺伝子Rev-erbαの役割2017

    • Author(s)
      大塚剛司、向阪 彰、辻本敬之、テン ソーレン、中尾友美、レ ティ フォエ、前田正信
    • Organizer
      第110回近畿生理学談話会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Heart-Specific Disruption of Bmal1 Leads to Hepatic Insulin Resistance in Mice.2017

    • Author(s)
      Nakao T, Kohsaka A, Le T H, Otsuka T, Thein L Z, Sato F, Ihara H, Maeda M
    • Organizer
      Experimental Biology
    • Related Report
      2017 Annual Research Report
  • [Presentation] 心臓特異的な時計遺伝子Bmal1の欠損は肝臓のインスリン抵抗性を惹起する2017

    • Author(s)
      中尾友美、向阪 彰、レ ティ フォエ、大塚剛司、テン ソーレン、佐藤冬樹、井原勇人、前田正信
    • Organizer
      第90回日本内分泌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Transcriptome analysis reveals dysregulation of genes associated with neuronal development and mood regulation in the prefrontal cortex of Rev-erbα deficient mice2016

    • Author(s)
      大塚剛司、向阪 彰、レ ティ フォエ、中尾友美、テン ソーレン、前田正信
    • Organizer
      第23回日本時間生物学会
    • Place of Presentation
      名古屋大学
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
  • [Presentation] トランスクリプトーム解析を用いたRev-erbαノックアウトマウスの情動行動異常の原因探索2016

    • Author(s)
      大塚剛司, 向阪彰, レ ティ フォエ, 中尾友美, テン ソーレン, 前田正信
    • Organizer
      第109回近畿生理学談話会
    • Place of Presentation
      大阪市立大学
    • Year and Date
      2016-11-05
    • Related Report
      2016 Research-status Report
  • [Presentation] Effect of the disrupted behavioral rhythm on mood and rhythmic expression of genes in the prefrontal cortex of mice2016

    • Author(s)
      H. T. Le, T. Otsuka, A. Kohsaka, T. Nakao, Z. L. Thein, M. Maeda
    • Organizer
      第109回近畿生理学談話会
    • Place of Presentation
      大阪市立大学
    • Year and Date
      2016-11-05
    • Related Report
      2016 Research-status Report
  • [Presentation] Expression profile of mood-related genes in the prefrontal cortex of Rev-erbα deficient mice.2016

    • Author(s)
      T. Otsuka, A. Kohsaka, H. T. Le, M. Maeda
    • Organizer
      17th Asian Australasian Animal Production
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      2016-08-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Rev-erbα deficiency is associated with mixed affective behaviors in mice.2016

    • Author(s)
      T. Otsuka, A. Kohsaka, H. T. Le, M. Maeda
    • Organizer
      Society for Research on Biological Rhythms
    • Place of Presentation
      Palm harbor, Florida, USA
    • Year and Date
      2016-05-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2019-03-29  

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