The drug development and identification of risk factor through animal model of 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。大鼠新生儿海马腹侧（NVH）病变被认为是一种假定的精神分裂症模型，其特征是在青春期后对应激和神经猝睡反应发生改变。本研究采用免疫组化和免疫印迹法检测青春期后NVH大鼠前额皮质（PFC） NRG-1、erbB4受体水平及其信号转导。定量分析显示，与假对照组相比，青春期后nvh损伤的动物PFC中NRG-1和erbB4磷酸化水平显著降低。NRG-1微注射NVH损伤大鼠PFC可减轻脉冲前抑制（PPI）缺陷。这些结果表明，PFC erbB4信号异常可能在NVH损伤大鼠PPI缺陷中起重要作用。NRG-1/erbB4信号可能成为治疗精神分裂症的新靶点。

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.