The involvement of phosphatidylinositol system in a rat model of schizophrenia

磷脂酰肌醇系统在大鼠精神分裂症模型中的参与

• 批准号: 21591526
• 负责人: NORIYAMA Yoshinobu
• 金额: $ 3.08万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591526/
• 关键词: 統合失調症; フォスファチジルイノシトール; ドパミン; PI-PLC; social isolation; 生理学; 脳・神経

First we examined the effect of SKF83959, Phosphatidylinositol-linked D1 receptor agonist, on synaptic transmission in CA1 area of mouse hippocampus. Spontaneous inhibitory postsynaptic currents recorded on pyramidal cells was enhanced by SKF83959.Then we decided to utilize'social isolation model'(SI-model) mice as a schizophrenia animal model. In behavioral tests, the reduction of prepulse inhibition and the decrease of percent alteration in Y-maze task were revealed, and we accepted these mice as schizophrenia animal model. Next we performed the electrophysiological recording to clarify certain abnormalities in a local neural circuit of SI-model mice. We recorded excitatory postsynaptic currents(EPSCs) and inhibitory postsynaptic currents(IPSCs) from pyramidal cells in layer 5 of mouse prefrontal cortex. The frequencies of the both spontaneous EPSCs and miniature EPSCs were lower in SI-model mice than control mice, whereas there was no significant difference between SI-model and control in spontaneous IPSCs. However, as we hypothesize alterations of the excitability of GABAergic interneurons, we next plan to directly record from interneurons to detect alterations of the membrane property. Following the comprehensive identification of the abnormalities of neural circuits in SI-model mouse, we plan to examine the therapeutic response of chronic administration of SKF83959 against aberrant neural circuits in SI-model mice PFC.

首先，我们检测了磷脂酰肌醇连接D1受体激动剂SKF83959对小鼠海马CA1区突触传递的影响。在锥体细胞上记录的自发抑制性突触后电流被SKF83959增强。然后我们决定利用“社会隔离模型”（SI-model）小鼠作为精神分裂症的动物模型。行为学实验显示，小鼠脉冲前抑制减弱，y型迷宫任务改变率下降，并将其作为精神分裂症动物模型。接下来，我们进行了电生理记录，以澄清si模型小鼠局部神经回路的某些异常。我们记录了小鼠前额叶皮层第5层锥体细胞的兴奋性突触后电流（EPSCs）和抑制性突触后电流（IPSCs）。si模型小鼠的自发性EPSCs和微型EPSCs的频率均低于对照组，而si模型小鼠的自发性IPSCs与对照组无显著差异。然而，当我们假设gaba能中间神经元的兴奋性改变时，我们下一步计划直接记录中间神经元以检测膜性质的改变。在全面确定si -模型小鼠神经回路异常后，我们计划检测长期给药SKF83959对si -模型小鼠PFC异常神经回路的治疗反应。

项目成果

新生マウス海馬でのドパミンによるGABA作動性介在性ニューロンの興奮性の増強

多巴胺增强新生小鼠海马 GABA 能中间神经元的兴奋性

• 发表时间: 2010
• 作者: Okahara K;Ishida Y;Hayashi Y;Inoue T;Tsuruta K;Takeuchi K;Yoshimuta H;Kiue K;Ninomiya Y;Kawano J;Yoshida K;Noda S;Tomita S;Fujimoto M;Hosomi J;Mitsuyama Y;Itoh K;中川恵樹
• 通讯作者: 中川恵樹

Enhancement of GABAergic interneuron excitability by dopamine in neonatal mouse hippocampus

多巴胺增强新生小鼠海马 GABA 能中间神经元兴奋性

• 发表时间: 2009
• 作者: K. Nakagawa;Y. Ogawa;H. Yoshino;Y. Noriyama;et al.
• 通讯作者: et al.

興奮性・抑制性シナプス伝達に対するドパミンの効果

多巴胺对兴奋性和抑制性突触传递的影响

• 发表时间: 2009
• 期刊: 脳と精神の医学
• 作者: Canuet L;Ikezawa K;Ishii R;Aoki Y ;Iwase M;Takeda M.;Shinno H;法山良信
• 通讯作者: 法山良信