Wang Xiao-Dong, Su Yun-Ai, Guo Chun-Mei, Yang Yang, Si Tian-Mei
Department of Psychopharmacology, Institute of Mental Health, Peking University, Beijing, China.
Int J Neuropsychopharmacol. 2008 Jun;11(4):553-61. doi: 10.1017/S1461145707008371. Epub 2008 Jan 10.
Neuregulin 1 (NRG1) has been identified as a susceptibility gene for schizophrenia, and dysregulation of NRG1 and its ErbB receptors is implicated in the pathophysiology of the disorder. The present study examined the protein expression levels of NRG1beta, ErbB2, ErbB3 and ErbB4 in the rat prefrontal cortex and hippocampus following a 4-wk administration of haloperidol (1 mg/kg i.p.), clozapine (10 mg/kg i.p.), or risperidone (1 mg/kg i.p.) by using immunohistochemistry and Western blot. The results showed that haloperidol promoted the expression of NRG1beta and ErbB4, whereas clozapine inhibited NRG1beta expression in the rat prefrontal cortex. Both haloperidol and clozapine significantly increased the protein levels of NRG1beta and ErbB receptors in the rat hippocampus. Repeated administration of risperidone only increased the expression of NRG1beta and ErbB4 in the hippocampus. Our findings demonstrate that antipsychotic drugs differentially regulate the expression of NRG1 and ErbB receptors in the rat brain, which may provide insight into the molecular basis of the pharmacological profile of antipsychotic drugs.
神经调节蛋白1（NRG1）已被确定为精神分裂症的一个易感基因，NRG1及其ErbB受体的失调与该疾病的病理生理学有关。本研究通过免疫组织化学和蛋白质印迹法，检测了大鼠经4周腹腔注射氟哌啶醇（1毫克/千克）、氯氮平（10毫克/千克）或利培酮（1毫克/千克）后，前额叶皮质和海马体中NRG1β、ErbB2、ErbB3和ErbB4的蛋白表达水平。结果显示，氟哌啶醇促进了大鼠前额叶皮质中NRG1β和ErbB4的表达，而氯氮平抑制了该区域NRG1β的表达。氟哌啶醇和氯氮平均显著增加了大鼠海马体中NRG1β和ErbB受体的蛋白水平。重复注射利培酮仅增加了海马体中NRG1β和ErbB4的表达。我们的研究结果表明，抗精神病药物对大鼠脑中NRG1和ErbB受体的表达有不同的调节作用，这可能为抗精神病药物药理特性的分子基础提供见解。
