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

点击翻译按钮获取中文摘要

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.