Almey Anne, Milner Teresa A, Brake Wayne G
Centre for Studies in Behavioral Neurobiology (CSBN), Department of Psychology, Concordia University, Montreal, QC, Canada.
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA; Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA.
Neurosci Lett. 2016 May 27;622:118-23. doi: 10.1016/j.neulet.2016.04.023. Epub 2016 Apr 11.
Estrogens affect dopamine transmission in the striatum, increasing dopamine availability, maintaining D2 receptor density, and reducing the availability of the dopamine transporter. Some of these effects of estrogens are rapid, suggesting that they are mediated by membrane associated receptors. Recently our group demonstrated that there is extra-nuclear labeling for ERα, ERβ, and GPER1 in the striatum, but that ERα and GPER1 are not localized to dopaminergic neurons in this region. GABAergic neurons are the most common type of neuron in the striatum, and changes in GABA transmission affect dopamine transmission. Thus, to determine whether ERα or GPER1 are localized to GABAergic neurons, we double labeled the striatum with antibodies for ERα or GPER1 and GABA and examined them using electron microscopy. Ultrastructural analysis revealed that ERα and GPER1 are localized exclusively to extranuclear sites in the striatum, and ∼35% of the dendrites and axon terminals labeled for these receptors contain GABA immunoreactivity. Binding at membrane-associated ERα and GPER1 could account for rapid estrogen-induced decreases in GABA transmission in the striatum, which, in turn, could affect dopamine transmission in this region.
雌激素影响纹状体中的多巴胺传递，增加多巴胺的可利用性，维持D2受体密度，并降低多巴胺转运体的可利用性。雌激素的这些作用有些是快速的，这表明它们是由膜相关受体介导的。最近我们小组证明，纹状体中存在雌激素受体α（ERα）、雌激素受体β（ERβ）和G蛋白偶联雌激素受体1（GPER1）的核外标记，但ERα和GPER1并不定位于该区域的多巴胺能神经元。γ-氨基丁酸能（GABAergic）神经元是纹状体中最常见的神经元类型，GABA传递的变化会影响多巴胺传递。因此，为了确定ERα或GPER1是否定位于GABAergic神经元，我们用针对ERα或GPER1和GABA的抗体对纹状体进行双重标记，并使用电子显微镜进行检查。超微结构分析显示，ERα和GPER1仅定位于纹状体的核外部位，标记这些受体的树突和轴突终末中约35%含有GABA免疫反应性。膜相关的ERα和GPER1上的结合可能解释了雌激素快速诱导的纹状体中GABA传递减少，这反过来又可能影响该区域的多巴胺传递。
