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Intranuclear molecular pathology of schizophrenia

Research Project

Project/Area Number 17K16367
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Psychiatric science
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Shiwaku Hiroki  東京医科歯科大学, 大学院医歯学総合研究科, 助教 (90747502)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords統合失調症 / 精神疾患 / DNAダメージ / シナプス / クロマチン / DNA損傷
Outline of Final Research Achievements

There are some patients with schizophrenia who cannot be sufficiently treated with the current therapeutic agents. It is necessary to establish and validate new pathological hypotheses. In this study, We analyzed the double-strand break of DNA damage in schizophrenia. Using mouse model of schizophrenia by PCP, we identified the double-strand breaks in PV neurons in hippocampus. As a result, we found that gene expression in PV neuron was suppressed. These damages may accumulate to form the symptoms of schizophrenia.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、すでに提唱されている統合失調症病態だけでは理解及び治療が不十分な、残遺状態に至る進行性・蓄積性の統合失調症の認知機能障害及び陰性症状の分子病態について、これまでに触れられていないDNA二重鎖切断病態が提唱された。統合失調症は、人口の約1%が罹患し、難治な場合もある精神疾患である。そのため、本研究により、DNAダメージを抑制する治療方法が確立されれば、統合失調症の残遺状態に至らないようにする治療戦略や、至った後でも回復を促す新たな治療戦略が生まれるかもしれない。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (9 results)

All 2020 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Detection of autoantibodies against GABAARα1 in patients with schizophrenia.2020

    • Author(s)
      Shiwaku H, Nakano Y, Kato M, Takahashi H.
    • Journal Title

      Schizophr Res.

      Volume: 216 Pages: 543-546

    • DOI

      10.1016/j.schres.2019.10.007

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of Tandospirone, a Partial Agonist of the 5-HT1A Receptor, in a Patient With Chronic Poststroke Emotional Incontinence With Anxiousness.2019

    • Author(s)
      Tamura T, Shiwaku H, Jitoku D, Kurumaji A.
    • Journal Title

      Prim Care Companion CNS Disord.

      Volume: 21(5) Issue: 5

    • DOI

      10.4088/pcc.18l02403

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Donepezil により精神病症状を伴う重症うつ病エピソードが誘発された1例2019

    • Author(s)
      塩飽裕紀、田村赳紘、治徳大介、車地暁生、西川徹
    • Journal Title

      精神科治療学

      Volume: 34 Pages: 231-236

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Paroxetine ameliorates whole-body allodynia.2018

    • Author(s)
      Shiwaku H, Nishikawa T
    • Journal Title

      Eur J Clin Pharmacol.

      Volume: 74 Issue: 7 Pages: 979-980

    • DOI

      10.1007/s00228-018-2438-0

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phencyclidine-induced dysregulation of primary cilia in the rodent brain.2017

    • Author(s)
      Shiwaku H, Umino A, Umino M, Nishikawa T.
    • Journal Title

      Brain Research

      Volume: 1674 Pages: 62-69

    • DOI

      10.1016/j.brainres.2017.08.022

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Developmental YAPdeltaC determines adult pathology in a model of spinocerebellar ataxia type 1.2017

    • Author(s)
      Fujita K, Mao Y, Uchida S, Chen X, Shiwaku H, Tamura T, Ito H, Watase K, Homma H, Tagawa K, Sudol M, Okazawa H.
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 1864-1864

    • DOI

      10.1038/s41467-017-01790-z

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Effect of Tandospirone, a Partial Agonist of the 5-HT1A Receptor, in a Patient With Chronic Poststroke Emotional Incontinence With Anxiousness.2019

    • Author(s)
      Hiroki Shiwaku, Yuri Nakano, Hidehiko Takahashi
    • Organizer
      Australasian Neuroscience society annual scientific meeting 2019.12.04 Aderaide
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ドネペジルにより精神病症状を伴う重症うつ病エピソードが誘発された1例2018

    • Author(s)
      塩飽裕紀、田村赳紘、治徳大介、車地暁生、西川徹
    • Organizer
      第114回 日本精神神経学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] ROSS 症候群における片側の脱力発作と脳幹の新規アセチルコリン病態2017

    • Author(s)
      塩飽裕紀、西川徹
    • Organizer
      第39回日本生物学的精神医学会・第47回日本神経精神薬理学会合同年会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-03-11  

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