The drug development and identification of risk factor through animal model of schizophrenia

2009 Fiscal Year Final Research Report

• Project/Area Number: 20790309
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Tohoku Pharmaceutical University
• Principal Investigator: NAKAGAWASAI Osamu Tohoku Pharmaceutical University, 薬学部, 助教 (50296018)
• Project Period (FY): 2008 – 2009
• Keywords: 統合失調症モデル動物 / 前頭前皮質 / ニューレグリン / 神経発達障害

Research Abstract

Recent molecular genetics studies in human have implicated the gene encoding neuregulin-1 (NRG-1) as a candidate susceptibility gene for schizophrenia. Neonatal ventral hippocampal (NVH) lesions in rats have been considered as a putative model of schizophrenia with characteristic post-pubertal alteration in response to stress and neuloleptics. In this study, we examined the levels of NRG-1, erbB4 receptors and the receptor's signaling in prefrontal cortex (PFC) of post-pubertal rats with NVH lesions, by using immunohistochemical and immunoblotting analyses. Quantitative analyses revealed that post-pubertal NVH-lesioned animals display significantly decreased levels of NRG-1 and erbB4 phosphorylation in PFC compared to sham controls. Microinjection of NRG-1 to PFC of NVH lesioned rats attenuated deficits in prepulse inhibition (PPI). These results that abnormal of erbB4 signaling in the PFC may play important roles in PPI deficits in NVH lesioned rats. NRG-1/erbB4 signaling may be novel therapeutic targets for schizophrenia.

Research Products

• [Journal Article] Behavioral and neurochemical characterization of mice deficient in the N-type Ca^<2+> channel alpha1B subunit (2010)
  • Author(s): Nakagawasai O, Onogi H, Mitazaki S, Sato A, Watanabe K, Saito H, Murai S, Nakaya K, Murakami M, Takahashi E, Tan-No K, Tadano T
  • Journal Title: Behav Brain Res 208 Pages: 224-230
  • Peer Reviewed
• [Journal Article] Central administration of p-hydroxyamphetamine produces a behavioral stimulant effect in rodents: evidence for the involvement of dopaminergic systems (2010)
  • Author(s): Onogi H, Hozumi M, Nakagawasai O, Arai Y, Ishigaki S, Sato A, Furuta S, Niijima F, Tan-No K, Tadano T
  • Journal Title: Psychopharmacology 208 Pages: 323-331
  • Peer Reviewed
• [Presentation] 幼若期腹側海馬障害雌性ラットにおける性周期依存的なプレパルスインヒビションの変化 (2010)
  • Author(s): 小野木弘志、中川西修、佐藤敦、中谷孝太、荒井裕一朗、新島富紀枝、丹野孝一、只野武
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-03-18
• [Presentation] メマンチンの感覚運動制御機構に及ぼす影響 (2010)
  • Author(s): 中谷孝太、中川西修、小野木弘志、佐藤敦、新島富紀枝、丹野孝一、只野武
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-03-18
• [Presentation] Serotonergic functions in a neurodevelopment model of schizophrenia (2008)
  • Author(s): Nakagawasai O, Mitazaki S, Onogi H, Watanabe K, Sato A, Niijima F, Tan-No K, Miyamoto A, Tadano T
  • Organizer: The XXVI CINP Congress
  • Place of Presentation: Munich, Germany
  • Year and Date: 2008-07-16
• [Remarks]
  • URL: http://www.tohoku-pharm.ac.jp/laboratory/yakuri/index.html