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Identification of drug target for novel antipsychotics based on proteomic approach

Research Project

Project/Area Number 21790067
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionNagoya University

Principal Investigator

NAGAI Taku  Nagoya University, 医学部附属病院, 准教授 (10377426)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords薬理学 / 脳・神経 / 神経化学 / 基礎研究 / 蛋白質 / プロテオーム / 統合失調症 / グルタミン酸受容体 / 神経科学
Research Abstract

Repeated administration of phencyclidine (PCP) has known to produces schizophrenic-like symptoms in mice. To examine the changes in protein expression after repeated PCP treatment in the prefrontal cortex (PFC) of mice, we performed proteomic analysis by using 2D-DIGE. Proteomic analysis reveals that the remarkable change in the expression levels of 14-3-3 protein θ was observed in the PFC after repeated treatment with PCP. The signals was localized to cells positive for S100, a marker of glial cells, in the PFC. Microinjection of 14-3-3 protein inhibitor into the PFC lead to memory impairment in a novel object recognition test. These results suggest that dysfunction of 14-3-3 protein θ in the PFC may be involved in the molecular mechanisms underlying the schizophrenic-like symptoms in repeated PCP-treated mice.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (25 results)

All 2010 2009 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (10 results) Book (3 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Chronic restraint stress impairs neurogenesis and hippocampus-dependent fear memory in mice2010

    • Author(s)
      Yun, J., Koike, H., Ibi, D., Toth, E., Mizoguchi, H., Nitta, A., Yoneyama, M., Ogita, K.Yoneda, Y., Nabeshima, T., Nagai, T., Yamada, K.
    • Journal Title

      Possible involvement of a brain-specific transcription factor Npas4.J.Neurochem 114

      Pages: 1840-1851

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nicotine ameliorates emotional and cognitive impairments induced by neonatal polyI2010

    • Author(s)
      Yu, J., Nagai, T., Ibi, D., Kitahara, Y., Nabeshima, T., Yamada, K.
    • Journal Title

      C treatment in mice.Open Behav.Sci.J. 4

      Pages: 9-18

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dysfunction of dopamine release in the prefrontal cortex of dysbindin deficient sandy mice2010

    • Author(s)
      Nagai, T., Kitahara, Y., Shiraki, A., Hikita, T., Taya, S., Kaibuchi, K., Yamada, K.
    • Journal Title

      an in vivo microdialysis study.Neurosci.Lett 470

      Pages: 134-138

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dysfunction of dopamine release in the prefrontal cortex of dysbindin deficient sandy mice : an in vivo microdialysis study.2010

    • Author(s)
      Nagai T, et al.
    • Journal Title

      Neurosci.Lett.

      Volume: 470 Pages: 134-138

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nicotine ameliorates emotional and cognitive impairments induced by neonatal polyI : C treatment in mice.2010

    • Author(s)
      Yu J, et al
    • Journal Title

      Open Behav.Sci.J.

      Volume: 4 Pages: 9-18

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic restraint stress impairs neurogenesis and hippocampus-dependent fear memory in mice : Possible involvement of a brain-specific transcription factor Npas4.2010

    • Author(s)
      Yun, et al
    • Journal Title

      J.Neurochem.

      Volume: 114 Pages: 1840-1851

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dysfunction of dopamine release in the prefrontal cortex of dysbindin deficient sandy mice : an in vivo microdialysis study.2010

    • Author(s)
      Nagai T, et al.
    • Journal Title

      Neurosci. Lett. 470

      Pages: 134-138

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aripiprazole ameliorates phencyclidine-induced impairment of recognition memory through dopamine D1 and serotonin 5-HT1A receptors.2009

    • Author(s)
      Nagai, T., Murai, R., Matsui, K., Kamei, H., Noda, Y., Furukawa, H., Nabeshima, T.
    • Journal Title

      Psychopharmacology 202

      Pages: 315-328

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aripiprazole ameliorates phencyclidine- induced impairment of recognition memory through dopamine D_1 and serotonin 5-HT_<1A> receptors.2009

    • Author(s)
      Nagai T, et al.
    • Journal Title

      Psychopharmacology 202

      Pages: 315-328

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 新生仔期polyI:C処置によって誘発される不安様行動および学習記憶障害2010

    • Author(s)
      永井拓, 于静華, 北原裕子, 衣斐大祐, 鍋島俊隆, 山田清文
    • Organizer
      第20回日本医療薬学会年会
    • Place of Presentation
      千葉
    • Related Report
      2010 Final Research Report
  • [Presentation] Methamphetamine increased Npas4, a neuronal PAS domain 4 expression; a possible role in neurite outgrowth and phosphorylated synapsin I expression.2010

    • Author(s)
      永井拓, 山田清文
    • Organizer
      第45回日本アルコール・薬物医学会、第22回日本アルコール精神医学会、第13回ニコチン・薬物依存研究フォーラム、2010アルコール・薬物依存関連学会合同学術総会
    • Place of Presentation
      小倉
    • Related Report
      2010 Final Research Report
  • [Presentation] 周産期の免疫異常が神経精神発達におよぼす影響(シンポジウム).2010

    • Author(s)
      永井拓, 衣斐大祐, 鍋島俊隆, 澤明, 山田清文
    • Organizer
      Neuro2010第33回日本神経科学大会、第53回日本神経化学会大会、第20回日本神経回路学会大会
    • Place of Presentation
      神戸
    • Related Report
      2010 Final Research Report
  • [Presentation] 周産期の免疫異常が神経精神発達におよぼす影響(シンポジウム)2010

    • Author(s)
      永井拓
    • Organizer
      Neuro2010第33回日本神経科学大会、第53回日本神経化学会大会、第20回日本神経回路学会大会
    • Place of Presentation
      神戸
    • Related Report
      2010 Annual Research Report
  • [Presentation] Methamphetamine increased Npas4, a neuronal PAS domain 4 expression ; a possible roic in neurite outgrowth and phosphorylated synapsin I expression.2010

    • Author(s)
      永井拓
    • Organizer
      第45回日本アルコール・薬物医学会、第22回日本アルコール精神医学会、第13回ニコチン・薬物依存研究フォーラム、平成22年度アルコール・薬物依存関連学会合同学術総会
    • Place of Presentation
      小倉
    • Related Report
      2010 Annual Research Report
  • [Presentation] 新生仔期polyI : C処置によって誘発される不安様行動および学習記憶障害2010

    • Author(s)
      永井拓
    • Organizer
      第20回日本医療薬学会年会
    • Place of Presentation
      千葉
    • Related Report
      2010 Annual Research Report
  • [Presentation] Neonatal polyI:C treatment in mice induces schizophrenia-like behavioral and neurochemical abnormalities in adulthood.2009

    • Author(s)
      Nagai, T., Ibi, D., Mizoguchi, H., Nabeshima, T., Yamada, K.
    • Organizer
      Neuroscience 2009, the 39th annual meeting of the Society for Neuroscience.
    • Place of Presentation
      Chicago, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] ニコチンの報酬効果における組織プラスミノーゲン活性化因子の関与(シンポジウム)2009

    • Author(s)
      永井拓, 鍋島俊隆, 山田清文
    • Organizer
      第44回日本アルコール・薬物医学会、第21回日本アルコール精神医学会、第12回ニコチン・薬物依存研究フォーラム2009合同学術総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] ニコチンの報酬効果における組織プラスミノーゲン活性化因子の関与(シンポジウム)2009

    • Author(s)
      永井拓
    • Organizer
      第44回日本アルコール・薬物医学会、第21回日本アルコール精神医学会、第12回ニコチン・薬物依存研究フォーラム平成21年度合同学術総会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] Neonatal polyI : C treatment in mice induces schizophrenia-like behavioral and neurochemical abnormalities in adulthood.2009

    • Author(s)
      Nagai T
    • Organizer
      Neuroscience 2009, the 39th annual meeting of the Society for Neuroscience.
    • Place of Presentation
      Chicago, USA
    • Related Report
      2009 Annual Research Report
  • [Book] 第II編第4章報酬機構関連3依存性薬物による精神障害の分子機序「実践行動薬理学」(編集・(社)日本薬理学会編集責任者・武田弘志,辻稔,赤池昭紀)2010

    • Author(s)
      永井拓, 鍋島俊隆, 山田清文
    • Publisher
      金芳堂
    • Related Report
      2010 Final Research Report
  • [Book] 実験薬理学シリーズ「実践行動薬理学」2010

    • Author(s)
      日本薬理学会編
    • Total Pages
      363
    • Publisher
      金芳堂
    • Related Report
      2010 Annual Research Report
  • [Book] 実験薬理学シリーズ「実践行動薬理学」2010

    • Author(s)
      日本薬理学会編
    • Publisher
      金芳堂(印刷中)
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.nagoya-u.ac.jp/pharmacy/02/index.html

    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] 統合失調症マーカー及びその利用2010

    • Inventor(s)
      尾崎紀夫, 永井拓, 吉見陽, 山田真之亮
    • Industrial Property Rights Holder
      国立大学法人名古屋大学
    • Industrial Property Number
      2010-147017
    • Filing Date
      2010-06-29
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] 統合失調症マーカー及びその利用2010

    • Inventor(s)
      尾崎紀夫, 永井拓, 吉見陽,山田真之亮
    • Industrial Property Rights Holder
      名古屋大学
    • Industrial Property Number
      2010-147017
    • Filing Date
      2010-06-29
    • Related Report
      2010 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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