Identification of drug target for novel antipsychotics based on proteomic approach

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790067
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Nagoya University
• Principal Investigator: NAGAI Taku Nagoya University, 医学部附属病院, 准教授 (10377426)
• Project Period (FY): 2009 – 2010
• 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

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.

Research Products

• [Journal Article] Chronic restraint stress impairs neurogenesis and hippocampus-dependent fear memory in mice (2010)
  • 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
  • Peer Reviewed
• [Journal Article] Nicotine ameliorates emotional and cognitive impairments induced by neonatal polyI (2010)
  • 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
  • Peer Reviewed
• [Journal Article] Dysfunction of dopamine release in the prefrontal cortex of dysbindin deficient sandy mice (2010)
  • 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
  • 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
  • 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
  • Year and Date: 20101113-20101114
• [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
  • Year and Date: 20101007-20101009
• [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
  • Year and Date: 20100902-20100904
• [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
  • Year and Date: 20091017-20091019
• [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
  • Year and Date: 20090907-20090909
• [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
  • Total Pages: 272-281
  • Publisher: 金芳堂
• [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: 特許,特願2010-147017
  • Filing Date: 2010-06-29