Vallée M, Mayo W, Koob G F, Le Moal M
INSERM U.259, Institut François Magendie, Domaine de Carreire, 33077 Bordeaux, France.
Int Rev Neurobiol. 2001;46:273-320. doi: 10.1016/s0074-7742(01)46066-1.
The discovery that neurosteroids could be synthesized de novo in the brain independent from the periphery and display neuronal actions led to great enthusiasm for the study of their physiological role. Pharmacological studies suggest that neurosteroids may be involved in several physiological processes, such as learning and memory. This chapter summarizes the effects of the administration of neurosteroids on learning and memory capabilities in rodents and in models of amnesia. We address the central mechanisms involved in mediating the modulation of learning and memory processes by neurosteroids. In this regard, the neurosteroid-modulated neurotransmitter systems, such as gamma-aminobutyric acid type A, N-methyl-D-aspartate, and cholinergic and sigma opioid systems, appear to be potential targets for the rapid memory alteration actions of neurosteroids. Moreover, given that some neurosteroids affect neuronal plasticity, this neuronal change could be involved in the long-term modulation of learning and memory processes. To understand the role of endogeneous neurosteroids in learning and memory processes, we present some physiological studies in rodents and humans. However, the latter do not successfully prove a role of endogenous neurosteroids in age-related memory impairments. Finally, we discuss the relative implication of a given neurosteroid vs its metabolites. For this question, a new approach using the quantitative determination of traces of neurosteroids by mass spectrometry seems to have potential for examining the role of each neurosteroid in discrete brain areas in learning and memory alterations, as observed during aging.
神经甾体能够在大脑中独立于外周从头合成并发挥神经元作用这一发现，引发了人们对其生理作用研究的极大热情。药理学研究表明，神经甾体可能参与多种生理过程，如学习和记忆。本章总结了给予神经甾体对啮齿动物和失忆模型学习与记忆能力的影响。我们阐述了介导神经甾体对学习和记忆过程调节作用的核心机制。在这方面，神经甾体调节的神经递质系统，如γ-氨基丁酸A型、N-甲基-D-天冬氨酸、胆碱能和σ阿片样物质系统，似乎是神经甾体快速改变记忆作用的潜在靶点。此外，鉴于一些神经甾体影响神经元可塑性，这种神经元变化可能参与学习和记忆过程的长期调节。为了解内源性神经甾体在学习和记忆过程中的作用，我们介绍了一些在啮齿动物和人类中的生理学研究。然而，后者未能成功证明内源性神经甾体在与年龄相关的记忆障碍中的作用。最后，我们讨论了特定神经甾体与其代谢产物的相对影响。对于这个问题，一种使用质谱法定量测定痕量神经甾体的新方法，似乎有潜力研究每种神经甾体在衰老过程中观察到的学习和记忆改变的离散脑区中的作用。
