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Reduced gene expression for Kv9.3 potassium channel subunit and cortical dysfunction in schizophrenia

Research Project

Project/Area Number 25293247
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Psychiatric science
Research InstitutionKanazawa University

Principal Investigator

Hashimoto Takanori  金沢大学, 医学系, 准教授 (40249959)

Co-Investigator(Kenkyū-buntansha) 戸田 重誠  金沢大学, 大学病院, 講師 (00323006)
吉原 亨  京都大学, 医学(系)研究科(研究院), 助教 (00401935)
上田 なつ子 (辻野 / 辻野 なつ子 / 上田 なつ子(辻野))  筑波大学, 国際統合睡眠医学研究機構, 助教 (40432166)
Research Collaborator Lewis David A  University of Pittsburgh, Department of Psychiatry and Neuroscience
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
Fiscal Year 2015: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywordsヒト死後脳 / 霊長類モデル / 遺伝子改変マウス / real-time PCR / in situ hybridization / 脳神経疾患 / 死後脳 / モデルマウス / 死後脳研究
Outline of Final Research Achievements

In the prefrontal cortex (PFC) of subjects with schizophrenia, alterations in parvalbumin (PV)-containing neurons are thought to contribute to cognitive deficits. Kv9.3 is a potassium channel subunit that is selectively expressed in PV neurons and critical to their roles in cognitive functions. Our cellular level quantification of the mRNA levels for KCNS3, the gene encoding Kv9.3, revealed that the number of KCNS3 mRNA-expressing neurons and the mRNA level per neuron were significantly reduced in the PFC of schizophrenia subjects. KCNS3 mRNA levels were unaffected in the PFC of monkeys exposed to antipsychotics, indicating that the lower KCNS3 expression is not solely due to the antipsychotic treatment. To test the effect of lower Kv9.3 subunit expression on cognitive functions, we inactivated the kcns3 gene in mice and confirmed reduced kcns3 mRNA expression in the PFC of these mice.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (11 results)

All 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Remarks (1 results)

  • [Int'l Joint Research] University of Pittsburgh(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Cortical gene expression after a conditional knockout of 67 kDa glutamic acid decarboxylase in parvalbumin neurons2016

    • Author(s)
      1.Georgiev D, Yoshihara T, Kawabata R, Matsubara T, Tsubomoto M, Minabe Y, Lewis DA, Hashimoto T
    • Journal Title

      Schizophrenia Bulletin

      Volume: 42 Pages: 992-1002

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Cortical gene expression after a conditional knockout of 67 kDa glutamic acid decarboxylase in parvalbumin neurons2016

    • Author(s)
      Georgiev D, Yoshihara T, Kawabata R, Matsubara T, Tsubomoto M, Minabe Y, Lewis DA, Hashimoto T
    • Journal Title

      Schizophrenia Bulletin

      Volume: in press Issue: 4 Pages: 992-1002

    • DOI

      10.1093/schbul/sbw022

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Reduced long-range functional connectivity in young children with autism spectrum disorder2015

    • Author(s)
      Kikuchi M, Yoshimura Y, Hiraishi H, Munesue T, Hashimoto T, Tsubokawa T, Takahashi T, Suzuki M, Higashida H, Minabe Y
    • Journal Title

      Soc Cogn Affect Neurosci

      Volume: 10 Pages: 248-254

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 死後脳研究と統合失調症2014

    • Author(s)
      坪本真 橋本隆紀
    • Journal Title

      精神科

      Volume: 25 Pages: 598-607

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Lower gene expression for KCNS3 potassium channel subunit in parvalbumin-containing neurons in the prefrontal cortex of subjects with schizophrenia2014

    • Author(s)
      Georgiev D, Arion D, Enwright JF, Kikuchi M, Minabe Y, Corradi JP, Lewis DA, Hashimoto T
    • Journal Title

      American Journal of Psychiatry

      Volume: 171 Pages: 62-71

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 統合失調症と大脳皮質パルブアルブミンニューロン2015

    • Author(s)
      橋本 隆紀
    • Organizer
      第37回生物学的精神医学会ランチョンセミナー
    • Place of Presentation
      東京タワーホール船堀
    • Year and Date
      2015-09-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 統合失調症における大脳皮質パルブアルブミンニューロン選択的遺伝子発現2015

    • Author(s)
      橋本 隆紀
    • Organizer
      第38回日本神経科学大会 国際シンポジウム「皮質GABA細胞の異常と精神神経疾患」
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2015-07-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 統合失調症の大脳皮質パルブアルブミンニューロンにおけるカリウムチャネル遺伝子発現2014

    • Author(s)
      橋本隆紀
    • Organizer
      日本生物学的精神医学会
    • Place of Presentation
      奈良県文化会館 (奈良県 奈良市)
    • Year and Date
      2014-09-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 統合失調症の認知機能障害の分子メカニズム:大脳皮質パルブアルブミン陽性ニューロンにおけるKCNS3遺伝子の発現変化

    • Author(s)
      橋本隆紀
    • Organizer
      第9回日本統合失調症学会 シンポジウム「次世代のトランスレーショナルリサーチ」
    • Place of Presentation
      京都テルサ
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Remarks] 統合失調症の認知障害にかかわる分子の減少を発見(Press Release)

    • URL

      http://www.kanazawa-u.ac.jp/university/administration/prstrategy/release/pdf/13/131030.pdf

    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2022-01-27  

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