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首页> 外文期刊>The Journal of toxicological sciences >Effects of prolonged antipsychotic administration on neuregulin-1/ErbB signaling in rat prefrontal cortex and myocardium: implications for the therapeutic action and cardiac adverse effect
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Effects of prolonged antipsychotic administration on neuregulin-1/ErbB signaling in rat prefrontal cortex and myocardium: implications for the therapeutic action and cardiac adverse effect

机译：长期服用抗精神病药对大鼠前额叶皮层和心肌中neuregulin-1 / ErbB信号传导的影响：对治疗作用和心脏不良反应的影响

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摘要

Patients with schizophrenia (SCZ) are at higher risk for developing cardiovascular disease (CVD) and neuregulin-1 (NRG1)/ErbB signaling has been identified as a common susceptibility pathway for the comorbidity. Antipsychotic treatment can change NRG1/ErbB signaling in the brain, which has been implicated in their therapeutic actions, whereas the drug-induced alterations of NRG1/ErbB pathway in cardiovascular system might be associated with the prominent cardiac side-effects of antipsychotic medication. To test this hypothesis, we examined NRG1/ErbB system in rat prefrontal cortex (PFC) and myocardium following 4-week intraperitoneal administration of haloperidol, risperidone or clozapine. Generally, the antipsychotics significantly enhanced NRG1/ErbB signaling with increased expression of NRG1 and phosphorylation of ErbB4 and ErbB2 in the brain and myocardium, except that clozapine partly blocked the cardiac NRG1/ErbB2 activation, which could be associated with its more severe cardiac adverse actions. Combined, our data firstly showed evidence of the effect of antipsychotic exposure on myocardial NRG1/ErbB signaling, along with the activated NRG1/ErbB system in brain, providing a potential link between the therapeutic actions and cardiotoxicity.
机译：精神分裂症（SCZ）患者患心血管疾病（CVD）的风险更高，而神经调节蛋白1（NRG1）/ ErbB信号传导已被确定为合并症的常见易感性途径。抗精神病药物治疗可以改变大脑中的NRG1 / ErbB信号传导，这与它们的治疗作用有关，而药物诱导的心血管系统NRG1 / ErbB途径的改变可能与抗精神病药物的显着心脏副作用有关。为了验证这一假设，我们在氟哌啶醇，利培酮或氯氮平腹膜内给药4周后，检查了大鼠前额叶皮层（PFC）和心肌中的NRG1 / ErbB系统。一般而言，抗精神病药会显着增强NRG1 / ErbB信号传导，并增强脑和心肌中NRG1的表达以及ErbB4和ErbB2的磷酸化，但氯氮平可部分阻断心脏NRG1 / ErbB2的激活，这可能与其更严重的心脏不良反应有关。结合起来，我们的数据首先显示了抗精神病药物暴露对心肌NRG1 / ErbB信号传导以及大脑中活化的NRG1 / ErbB系统的影响的证据，提供了治疗作用和心脏毒性之间的潜在联系。

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