Department of Histology, School of Medicine in Katowice, Medical University of Silesia, ul. Medyków Street 18, 40-752, Katowice, Poland.
Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YQ, UK.
J Mol Neurosci. 2019 Jun;68(2):311-317. doi: 10.1007/s12031-019-01307-x. Epub 2019 Apr 9.
Antipsychotic drugs, known as the antagonists of dopaminergic receptors, may also affect a large spectrum of other molecular signaling pathways in the brain. Despite the numerous ongoing studies on neurosteroid action and regulation, there are no reports regarding the influence of extended treatment with typical and atypical neuroleptics on brain aromatase (CYP19A1) expression. In the present study, we assessed for the first time aromatase mRNA and protein levels in the brain of rats chronically (28 days) treated with olanzapine, clozapine, and haloperidol using quantitative real-time PCR, end-point RT-PCR, and Western blotting. Both clozapine and haloperidol, but not olanzapine treatment, led to an increase of aromatase mRNA expression in the rat brain. On the other hand, aromatase protein level remained unchanged after drug administration. These results cast a new light on the pharmacology of examined antipsychotics and contribute to a better understanding of the mechanisms responsible for their action. The present report also underlines the complex nature of potential interactions between neuroleptic pharmacological effects and physiology of brain neurosteroid pathways.
抗精神病药物，被称为多巴胺受体拮抗剂，也可能影响大脑中其他大量的分子信号通路。尽管目前有许多关于神经甾体作用和调节的研究，但还没有关于长期使用典型和非典型神经安定药对大脑芳香酶（CYP19A1）表达影响的报道。在本研究中，我们首次使用定量实时 PCR、终点 RT-PCR 和 Western 印迹法评估了慢性（28 天）给予奥氮平、氯氮平和氟哌啶醇的大鼠脑内芳香酶 mRNA 和蛋白水平。氯氮平和氟哌啶醇治疗，但不是奥氮平治疗，导致大鼠脑内芳香酶 mRNA 表达增加。另一方面，药物治疗后芳香酶蛋白水平保持不变。这些结果为研究中的抗精神病药物的药理学提供了新的认识，并有助于更好地理解其作用的机制。本报告还强调了神经安定药药理学效应与脑神经甾体途径生理学之间潜在相互作用的复杂性。
