Maurice T, Urani A, Phan V L, Romieu P
Behavioural Neuropharmacology Group, INSERM U. 336, Institut de Biologie, 4 Bvd Henri IV, 34060, Montpellier, France.
Brain Res Brain Res Rev. 2001 Nov;37(1-3):116-32. doi: 10.1016/s0165-0173(01)00112-6.
Steroids, synthesized in peripheral glands or centrally in the brain--the latter being named neurosteroids--exert an important role as modulators of the neuronal activity by interacting with different receptors or ion channels. In addition to the modulation of GABA(A), NMDA or cholinergic receptors, neuroactive steroids interact with an atypical intracellular receptor, the sigma(1) protein. This receptor has been cloned in several species, and highly selective synthetic ligands are available. At the cellular level, sigma1 agonists modulate intracellular calcium mobilization and extracellular calcium influx, NMDA-mediated responses, acetylcholine release, and alter monoaminergic systems. At the behavioral level, the sigma1 receptor is involved in learning and memory processes, the response to stress, depression, neuroprotection and pharmacodependence. Pregnenolone, dehydroepiandrosterone, and their sulfate esters behave as sigma1 agonists, while progesterone is a potent antagonist. This review will detail the physiopathological consequences of these interactions, focusing on recent results on memory and depression. The therapeutical interest of selective sigma1 receptor agonists in alleviating aging-related cognitive deficits will be discussed.
类固醇在外周腺体或大脑中合成（后者被称为神经甾体），通过与不同受体或离子通道相互作用，作为神经元活动的调节剂发挥重要作用。除了调节GABA(A)、NMDA或胆碱能受体外，神经活性甾体还与一种非典型细胞内受体——sigma(1)蛋白相互作用。该受体已在多个物种中克隆出来，并且有高选择性的合成配体。在细胞水平上，sigma1激动剂调节细胞内钙动员和细胞外钙内流、NMDA介导的反应、乙酰胆碱释放，并改变单胺能系统。在行为水平上，sigma1受体参与学习和记忆过程、对应激的反应、抑郁、神经保护和药物依赖性。孕烯醇酮、脱氢表雄酮及其硫酸酯表现为sigma1激动剂，而孕酮是一种强效拮抗剂。本综述将详细阐述这些相互作用的生理病理后果，重点关注记忆和抑郁方面的最新研究结果。还将讨论选择性sigma1受体激动剂在缓解衰老相关认知缺陷方面的治疗意义。
