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神经甾体与临床精神病学的相关性:从实验室到床边

The relevance of neurosteroids to clinical psychiatry: from the laboratory to the bedside.

作者信息

Strous Rael D, Maayan Rachel, Weizman Abraham

机构信息

Beer Yaakov Mental Health Center, PO Box 1, Beer Yaakov 70350, Israel.

出版信息

Eur Neuropsychopharmacol. 2006 Apr;16(3):155-69. doi: 10.1016/j.euroneuro.2005.09.005. Epub 2005 Oct 27.

Abstract

Neurosteroids are important neuroactive molecules with suggested central involvement in several neurophysiological and psychiatric disease processes. The discovery of neurosteroids followed the revelation that the brain exhibited the capacity to synthesize its own steroids in situ and thus be a potential site of steroidogenesis. In contrast to some steroids that exhibit traditional genomic steroid actions, most neurosteroids appear to regulate neuronal function by means of "non-genomic" mechanisms influencing neuronal excitability. Neurosteroids are synthesized either from CNS cholesterol or from peripheral steroid precursors and exhibit a wide range of modulatory effects on neurotransmitter receptor activity, most notably at the gamma-aminobutyric acid A (GABA(A)) receptor. Neurosteroids play an important role in neurodevelopment and neuroprotective effects, many aspects of which may have particular applicability to psychiatric disorders including various gender differences. Neurosteroids appear to be relevant to the pathophysiology and pharmacological treatment of many psychiatric disorders including the most notable mood and anxiety disorders, but also psychotic, childhood, eating, dementia, stress and postpartum disorders. It has been suggested that neurosteroids may become potential targets for pharmacological intervention in the future with further neurosteroid investigation contributing to a more comprehensive understanding of human behavior and psychopathology.

摘要

神经甾体是重要的神经活性分子,据推测在几种神经生理和精神疾病过程中起核心作用。神经甾体的发现是在有证据表明大脑具有原位合成自身甾体的能力,因此可能是甾体生成的潜在部位之后。与一些表现出传统基因组甾体作用的甾体不同,大多数神经甾体似乎通过影响神经元兴奋性的“非基因组”机制来调节神经元功能。神经甾体可由中枢神经系统胆固醇或外周甾体前体合成,并对神经递质受体活性表现出广泛的调节作用,最显著的是对γ-氨基丁酸A(GABAA)受体。神经甾体在神经发育和神经保护作用中发挥重要作用,其中许多方面可能对包括各种性别差异在内的精神疾病具有特殊适用性。神经甾体似乎与许多精神疾病的病理生理学和药物治疗相关,包括最显著的情绪和焦虑障碍,还有精神病性、儿童期、饮食、痴呆、应激和产后障碍。有人提出,随着对神经甾体的进一步研究有助于更全面地理解人类行为和精神病理学,神经甾体未来可能成为药物干预的潜在靶点。

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