The endogenic neurosteroid system and its role in the pathogenesis and therapy of mental disorders

Q3 Pharmacology, Toxicology and Pharmaceutics

Research Results in Pharmacology Pub Date : 2023-03-31 DOI:10.18413/rrpharmacology.9.10015

S. P. Bairamova, D. Petelin, R. Akhapkin, N. Kudryashov, O. Sorokina, S. A. Semin, Veronika Panfilova, B. A. Volel

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引用次数: 2

Abstract

Introduction: Although neurosteroids have been relatively recently discovered, their significant role in the neurochemical processes and pathogenesis of a number of psychiatric and neurological disorders is now quite clear. First of all, it seems important to clarify the definition of the endogenous neurosteroids as a class of steroids, taking into account the variability of approaches to their description. Currently, neurosteroids include endogenous steroids synthesized in the central nervous system, gonads, or adrenal glands and interacting with GABAA, NMDA, and sigma-1 receptors. Neurosteroid biosynthesis: Biosynthesis of neurosteroids begins with rate-limiting reaction of TSPO binding cholesterol and transporting it into the mitochondria, where pregnenolone is synthesized following the cytochrome P450scc (CYP11A1) impact. Interaction with GABAА, NMDA and sigma-1 receptors: According to the experimental data, neurosteroids act as the most highly potent endogenous allosteric modulators of the GABA receptor; some types of neurosteroids (ALLO, DHEA, etc.) can produce a rapid anxiolytic and anticonvulsant effect. There is some experimental evidence for antipsychotic effects of some neurosteroids realized through NMDA receptors: intracerebral administration of ALLO to laboratory animals can prevent further appearance of motor agitation and other equivalents of psychosis after administration of high doses of amphetamines. It has also been proven in several studies on animal models that neurosteroids exhibit anxiolytic effects through sigma-1 receptors. Conclusion: The article describes the process of neurosteroidogenesis and the effect of neurosteroids on listed receptorsin accordance with already available scientific data. In addition, this paper describes the specific role of various neurosteroids in the development of mental illnesses, including anxiety disorders, depression, and schizophrenia Graphical Abstract

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内源性神经鞘瘤系统及其在精神障碍发病机制和治疗中的作用

引言：尽管神经甾体是最近才发现的，但它们在许多精神和神经疾病的神经化学过程和发病机制中的重要作用现在已经很清楚了。首先，考虑到描述方法的可变性，澄清内源性神经类固醇作为一类类固醇的定义似乎很重要。目前，神经类固醇包括在中枢神经系统、性腺或肾上腺合成的内源性类固醇，并与GABAA、NMDA和sigma-1受体相互作用。神经类固醇生物合成：神经类固醇的生物合成始于TSPO结合胆固醇的限速反应，并将其运输到线粒体中，在线粒体中，孕烯醇酮是在细胞色素P450scc（CYP11A1）影响下合成的。与GABAА、NMDA和sigma-1受体的相互作用：根据实验数据，神经类固醇是GABA受体最高效的内源性变构调节剂；某些类型的神经类固醇（ALLO、DHEA等）可以产生快速的抗焦虑和抗惊厥作用。有一些实验证据表明，一些神经类固醇通过NMDA受体实现了抗精神病作用：对实验动物脑内给予ALLO可以防止在给予高剂量的安非他命后进一步出现运动激动和其他类似的精神病。在几项关于动物模型的研究中也证明，神经类固醇通过sigma-1受体表现出抗焦虑作用。结论：根据已有的科学数据，本文描述了神经甾体发生的过程以及神经甾体对所列受体的影响。此外，本文还描述了各种神经类固醇在精神疾病发展中的具体作用，包括焦虑症、抑郁症和精神分裂症

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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