Estrogen facilitates higher cognitive functions by exerting effects on brain regions such as the prefrontal cortex and hippocampus. Estrogen induces spinogenesis and synaptogenesis in these two brain regions and also initiates a complex set of signal transduction pathways via estrogen receptors (ERs). Along with the classical genomic effects mediated by activation of ER α and ER β, there are membrane-bound ER α, ER β, and G protein-coupled estrogen receptor 1 (GPER1) that can mediate rapid nongenomic effects. All key ERs present throughout the body are also present in synapses of the hippocampus and prefrontal cortex. This review summarizes estrogen actions in the brain from the standpoint of their effects on synapse structure and function, noting also the synergistic role of progesterone. We first begin with a review of ER subtypes in the brain and how their abundance and distributions are altered with aging and estrogen loss (e.g., ovariectomy or menopause) in the rodent, monkey, and human brain. As there is much evidence that estrogen loss induced by menopause can exacerbate the effects of aging on cognitive functions, we then review the clinical trials of hormone replacement therapies and their effectiveness on cognitive symptoms experienced by women. Finally, we summarize studies carried out in nonhuman primate models of age- and menopause-related cognitive decline that are highly relevant for developing effective interventions for menopausal women. Together, we highlight a new understanding of how estrogen affects higher cognitive functions and synaptic health that go well beyond its effects on reproduction.

中文翻译：

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雌激素对生命全程认知和突触健康的影响。


雌激素通过对前额皮质和海马体等大脑区域产生影响来促进更高的认知功能。雌激素诱导这两个大脑区域的棘发生和突触发生，并通过雌激素受体（ER）启动一组复杂的信号转导途径。除了 ER α 和 ER β 激活介导的经典基因组效应外，膜结合的 ER α、ER β 和 G 蛋白偶联雌激素受体 1 (GPER1) 也可以介导快速的非基因组效应。全身存在的所有关键 ER 也存在于海马体和前额皮质的突触中。这篇综述从雌激素对突触结构和功能的影响的角度总结了雌激素在大脑中的作用，还指出了孕激素的协同作用。我们首先回顾大脑中的 ER 亚型，以及它们的丰度和分布如何随着啮齿动物、猴子和人类大脑中衰老和雌激素丧失（例如卵巢切除或更年期）而改变。由于有大量证据表明更年期引起的雌激素减少会加剧衰老对认知功能的影响，因此我们回顾了激素替代疗法的临床试验及其对女性认知症状的有效性。最后，我们总结了在与年龄和更年期相关的认知衰退的非人类灵长类动物模型中进行的研究，这些研究与针对更年期妇女制定有效的干预措施高度相关。我们共同强调了对雌激素如何影响高级认知功能和突触健康的新认识，其影响远远超出了其对生殖的影响。