Intranuclear molecular pathology of schizophrenia

• Project/Area Number: 17K16367
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Tokyo 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: ¥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。

Research Products

• [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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
• [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