Without medical progress, dementing diseases such as Alzheimer's disease will become one of the main causes of disability. Preventing or delaying them has thus become a real challenge for biomedical research. Steroids offer interesting therapeutical opportunities for promoting successful aging because of their pleiotropic effects in the nervous system: they regulate main neurotransmitter systems, promote the viability of neurons, play an important role in myelination and influence cognitive processes, in particular learning and memory. Preclinical research has provided evidence that the normally aging nervous system maintains some capacity for regeneration and that age-dependent changes in the nervous system and cognitive dysfunctions can be reversed to some extent by the administration of steroids. The aging nervous system also remains sensitive to the neuroprotective effects of steroids. In contrast to the large number of studies documenting beneficial effects of steroids on the nervous system in young and aged animals, the results from hormone replacement studies in the elderly are so far not conclusive. There is also little information concerning changes of steroid levels in the aging human brain. As steroids present in nervous tissues originate from the endocrine glands (steroid hormones) and from local synthesis (neurosteroids), changes in blood levels of steroids with age do not necessarily reflect changes in their brain levels. There is indeed strong evidence that neurosteroids are also synthesized in human brain and peripheral nerves. The development of a very sensitive and precise method for the analysis of steroids by gas chromatography/mass spectrometry (GC/MS) offers new possibilities for the study of neurosteroids. The concentrations of a range of neurosteroids have recently been measured in various brain regions of aged Alzheimer's disease patients and aged non-demented controls by GC/MS, providing reference values. In Alzheimer's patients, there was a general trend toward lower levels of neurosteroids in different brain regions, and neurosteroid levels were negatively correlated with two biochemical markers of Alzheimer's disease, the phosphorylated tau protein and the beta-amyloid peptides. The metabolism of dehydroepiandrosterone has also been analyzed for the first time in the aging brain from Alzheimer patients and non-demented controls. The conversion of dehydroepiandrosterone to Delta5-androstene-3beta,17beta-diol and to 7alpha-OH-dehydroepiandrosterone occurred in frontal cortex, hippocampus, amygdala, cerebellum and striatum of both Alzheimer's patients and controls. The formation of these metabolites within distinct brain regions negatively correlated with the density of beta-amyloid deposits.

中文翻译：

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类固醇激素和神经甾体在神经系统的正常和病理性衰老中。

没有医学上的进步，痴呆症如老年痴呆症将成为致残的主要原因之一。因此，预防或延迟它们已成为生物医学研究的真正挑战。甾类化合物因其对神经系统的多效作用而提供了促进成功衰老的有趣治疗机会：它们调节主要的神经递质系统，促进神经元的活力，在髓鞘形成中发挥重要作用并影响认知过程，特别是学习和记忆。临床前研究提供了证据，表明正常衰老的神经系统具有一定的再生能力，并且通过使用类固醇可以在一定程度上逆转年龄相关的神经系统变化和认知功能障碍。衰老的神经系统也对类固醇的神经保护作用敏感。与大量研究表明类固醇对幼年和老年动物的神经系统有有益作用的大量研究相反，迄今为止，老年人激素替代研究的结果尚无定论。关于衰老的人脑中类固醇水平变化的信息也很少。由于神经组织中存在的类固醇来源于内分泌腺体（类固醇激素）和局部合成物质（神经类固醇），因此类固醇的血液水平随年龄的变化不一定反映其大脑水平的变化。确实有确凿的证据表明，神经类固醇也可以在人脑和周围神经中合成。通过气相色谱/质谱法（GC / MS）开发一种非常灵敏，精确的类固醇分析方法，为神经类固醇的研究提供了新的可能性。最近，已通过GC / MS在老年阿尔茨海默氏病患者和老年非痴呆对照人群的各个大脑区域中测量了一系列神经类固醇的浓度，以提供参考值。在阿尔茨海默氏病患者中，不同脑区神经甾体水平普遍呈下降趋势，神经甾体水平与阿尔茨海默氏病的两个生化标志物磷酸化的tau蛋白和β-淀粉样蛋白肽呈负相关。还首次在阿尔茨海默氏病患者和非痴呆症对照组的衰老大脑中分析了脱氢表雄酮的代谢。在阿尔茨海默氏病患者和对照的额叶皮层，海马，杏仁核，小脑和纹状体中均发生了脱氢表雄酮向Delta5-雄烯-3β，17β-二醇和7α-OH-脱氢表雄酮的转化。这些代谢物在不同大脑区域的形成与β淀粉样蛋白沉积物的密度负相关。