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

精神分裂症动物模型的药物开发及危险因素识别

• 批准号: 20790309
• 负责人: NAKAGAWASAI Osamu
• 金额: $ 1.91万
• 依托单位: Tohoku Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790309/
• 关键词: 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; erbB4受容体; グルタミン酸受容体

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.

最近的人类分子遗传学研究表明，编码神经调节蛋白-1(NRG-1)的基因是精神分裂症的候选易感基因。新生大鼠海马腹侧区(NVH)损伤被认为是一种可能的精神分裂症模型，具有青春期后应激和神经感受剂的特征改变。本研究采用免疫组织化学和免疫印迹方法检测了青春期后NVH损伤大鼠前额叶皮质中NRG-1、ERBB4受体及其信号转导的水平。定量分析显示，青春期后NVH损伤动物的PFC中NRG-1和ERBB4的磷酸化水平显著低于假手术对照组。NVH损毁大鼠PFC内微量注射NRG-1可减轻脉冲前抑制(PPI)缺陷。这些结果表明，PFC中ERBB4信号的异常可能在NVH大鼠PPI缺陷中起重要作用。NRG-1/ERBB4信号通路可能成为治疗精神分裂症的新靶点。

项目成果

メマンチンの感覚運動制御機構に及ぼす影響

美金刚对感觉运动控制机制的影响

• 发表时间: 2010
• 作者: 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
• 通讯作者: 只野武

Behavioral and neurochemical characterization of mice deficient in theN-type Ca^<2+> channel alpha1B subunit

N型Ca^2>通道α1B亚基缺陷小鼠的行为和神经化学特征

• 发表时间: 2010
• 期刊: Behav Brain Res 208
• 作者: Nakagawasai O;(他11名)
• 通讯作者: (他11名)

Central administration of p-hydroxyamphetamine produces a behavioral stimulant effect in rodents: evidence for the involvement of dopaminergic systems

对羟基苯丙胺的中枢给药对啮齿类动物产生行为刺激作用：多巴胺能系统参与的证据

• 发表时间: 2010
• 期刊: Psychopharmacology 208
• 作者: Onogi H;Hozumi M;Nakagawasai O;Arai Y;Ishigaki S;Sato A;Furuta S;Niijima F;Tan-No K;Tadano T
• 通讯作者: Tadano T

Central administration of phydroxyamphetamine produces a behavioral stimulant effect in rodents : evidence for the involvement of dopaminergic systems

对羟基苯丙胺的中枢给药对啮齿类动物产生行为刺激作用：多巴胺能系统参与的证据

• 发表时间: 2010
• 期刊: Psychopharmacology 208
• 作者: Onogi H;Hozumi M;Nakagawasai O;(他7名)
• 通讯作者: (他7名)

Serotonergic functions in a neurodevelopment model of schizophrenia

精神分裂症神经发育模型中的血清素功能

• 发表时间: 2008
• 作者: Nakagawasai O;Mitazaki S;Onogi H;Watanabe K;Sato A;Niijima F;Tan-No K;Miyamoto A;Tadano T
• 通讯作者: Tadano T