雌激素在大脑和认知衰老中的作用。
The Role of Estrogen in Brain and Cognitive Aging.
机构信息
Department of Pharmacology, Vanderbilt University, Nashville, TN, 37232, USA.
Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, 37232, USA.
出版信息
Neurotherapeutics. 2019 Jul;16(3):649-665. doi: 10.1007/s13311-019-00766-9.
There are 3 common physiological estrogens, of which estradiol (E2) is seen to decline rapidly over the menopausal transition. This decline in E2 has been associated with a number of changes in the brain, including cognitive changes, effects on sleep, and effects on mood. These effects have been demonstrated in both rodent and non-human preclinical models. Furthermore, E2 interactions have been indicated in a number of neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, and depression. In normal brain aging, there are a number of systems that undergo changes and a number of these show interactions with E2, particularly the cholinergic system, the dopaminergic system, and mitochondrial function. E2 treatment has been shown to ameliorate some of the behavioral and morphological changes seen in preclinical models of menopause; however, in clinical populations, the effects of E2 treatment on cognitive changes after menopause are mixed. The future use of sex hormone treatment will likely focus on personalized or precision medicine for the prevention or treatment of cognitive disturbances during aging, with a better understanding of who may benefit from such treatment.
有 3 种常见的生理性雌激素，其中雌二醇（E2）在绝经过渡期间迅速下降。E2 的这种下降与大脑的许多变化有关，包括认知变化、对睡眠的影响以及对情绪的影响。这些影响在啮齿动物和非人类临床前模型中都得到了证实。此外，E2 的相互作用已在多种神经精神疾病中得到证实，包括阿尔茨海默病、精神分裂症和抑郁症。在正常的大脑衰老过程中，有许多系统会发生变化，其中许多系统与 E2 相互作用，特别是胆碱能系统、多巴胺能系统和线粒体功能。研究表明，E2 治疗可以改善绝经前临床前模型中观察到的一些行为和形态变化；然而，在临床人群中，E2 治疗对绝经后认知变化的影响是混杂的。未来性激素治疗的应用可能会集中在个性化或精准医学上，以预防或治疗衰老过程中的认知障碍，从而更好地了解谁可能受益于这种治疗。
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