Vallée M, Mayo W, Le Moal M
Institut F. Magendie-INSERM U259, Domaine de Carreire, Rue Camille Saint Saëns, 33077, Cedex, Bordeaux, France.
Brain Res Brain Res Rev. 2001 Nov;37(1-3):301-12. doi: 10.1016/s0165-0173(01)00135-7.
Aging is a general process of functional decline which involves in particular a decline of cognitive abilities. However, the severity of this decline differs from one subject to another and inter-individual differences have been reported in humans and animals. These differences are of great interest especially as concerns investigation of the neurobiological factors involved in cognitive aging. Intensive pharmacological studies suggest that neurosteroids, which are steroids synthesized in the brain in an independent manner from peripheral steroid sources, could be involved in learning and memory processes. This review summarizes data in animals and humans in favor of a role of neurosteroids in cognitive aging. Studies in animals demonstrated that the neurosteroids pregnenolone (PREG) and dehydroepiandrosterone (DHEA), as sulfate derivatives (PREGS and DHEAS, respectively), display memory-enhancing properties in aged rodents. Moreover, it was recently shown that memory performance was correlated with PREGS levels in the hippocampus of 24-month-old rats. Human studies, however, have reported contradictory results. First, improvement of learning and memory dysfunction was found after DHEA administration to individuals with low DHEAS levels, but other studies failed to detect significant cognitive effects after DHEA administration. Second, cognitive dysfunctions have been associated with low DHEAS levels, high DHEAS levels, or high DHEA levels; while in other studies, no relationship was found. As future research perspectives, we propose the use of new methods of quantification of neurosteroids as a useful tool for understanding their respective role in improving learning and memory impairments associated with normal aging and/or with pathological aging, such as Alzheimer's disease.
衰老作为一种普遍的功能衰退过程，尤其涉及认知能力的下降。然而，这种衰退的严重程度因人而异，人类和动物中均已报道了个体间的差异。这些差异特别引起人们的兴趣，尤其是在研究认知衰老所涉及的神经生物学因素方面。大量药理学研究表明，神经甾体（即独立于外周甾体来源在大脑中合成的甾体）可能参与学习和记忆过程。这篇综述总结了动物和人类中支持神经甾体在认知衰老中发挥作用的数据。动物研究表明，神经甾体孕烯醇酮（PREG）和脱氢表雄酮（DHEA）作为硫酸酯衍生物（分别为PREGS和DHEAS），在老年啮齿动物中具有增强记忆的特性。此外，最近研究表明，24月龄大鼠海马中的PREGS水平与记忆表现相关。然而，人类研究报告了相互矛盾的结果。首先，给DHEAS水平较低的个体服用DHEA后，发现学习和记忆功能障碍有所改善，但其他研究未能检测到服用DHEA后有显著的认知效果。其次，认知功能障碍与低DHEAS水平、高DHEAS水平或高DHEA水平相关；而在其他研究中，未发现相关性。作为未来的研究方向，我们建议使用新的神经甾体定量方法，作为理解它们在改善与正常衰老和/或病理性衰老（如阿尔茨海默病）相关的学习和记忆损伤中各自作用的有用工具。
