Kim Hyun Jin, Casadesus Gemma
Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44106, USA.
Biochim Biophys Acta. 2010 Oct;1800(10):1090-3. doi: 10.1016/j.bbagen.2010.05.001. Epub 2010 May 12.
A plethora of evidence supports a beneficial role of estrogen in the brain. However, while these effects are hypothesized to be driven via the two main forms of estrogen receptors (ERα and ERß), the mechanism through which these receptors mediate estrogen's effects on cognition and plasticity remain unclear. Estrogen receptors are heterogeneously expressed in many cognition sensitive regions of the brain, have the ability to dimerize and heterodimerize, and are localized to both neurons and glia. In addition, while many of the known actions of estrogen through their receptor are mediated via the classical genomic regulatory mechanism of gene transcription, rapid non-genomic action of estrogens are also gaining relevance. These complex events make the mechanistic understanding of estrogen effects challenging. The development of transgenic estrogen receptor knockout mouse models has provided some much needed insight on the role of these receptors in mediating estrogen effects on cognition and synaptic plasticity. This review provides an overview of estrogen receptors in the brain and an update of knowledge gained from transgenic knockout models on cognition and synaptic plasticity.
大量证据支持雌激素在大脑中发挥有益作用。然而，尽管推测这些作用是通过雌激素受体的两种主要形式（ERα和ERβ）介导的，但这些受体介导雌激素对认知和可塑性影响的机制仍不清楚。雌激素受体在大脑中许多对认知敏感的区域呈异质性表达，具有二聚化和异源二聚化的能力，并且定位于神经元和神经胶质细胞。此外，虽然雌激素通过其受体的许多已知作用是通过经典的基因转录基因组调控机制介导的，但雌激素的快速非基因组作用也越来越受到关注。这些复杂的事件使得对雌激素作用机制的理解具有挑战性。转基因雌激素受体敲除小鼠模型的发展为这些受体在介导雌激素对认知和突触可塑性影响中的作用提供了一些急需的见解。本综述概述了大脑中的雌激素受体，并更新了从转基因敲除模型中获得的关于认知和突触可塑性的知识。
