G-Protein-Coupled Estrogen Receptor 1 Is Anatomically Positioned to Modulate Synaptic Plasticity in the Mouse Hippocampus
G-Protein-Coupled Estrogen Receptor 1 Is Anatomically Positioned to Modulate Synaptic Plasticity in the Mouse Hippocampus
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DOI：
10.1523/jneurosci.1298-14.2015
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发表时间：
2015-02
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通讯作者：
E. Waters;L. Thompson;Parth Patel;Andreina D Gonzales;H. Z. Ye;E. Filardo;D. Clegg;Jolanta Gorecka-Jolanta-Gor
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作者：
E. Waters;L. Thompson;Parth Patel;Andreina D Gonzales;H. Z. Ye;E. Filardo;D. Clegg;Jolanta Gorecka-Jolanta-Gor
动情周期和性别都影响啮齿动物背海马中含有经典雌激素受体α和β的神经元和胶质细胞的数量和类型以及突触水平。在这里，我们研究了是否膜雌激素受体，G蛋白偶联雌激素受体1（GPER 1），是解剖学定位在背海马的小鼠调节突触可塑性。光镜下，GPER 1免疫反应（IR）在锥体细胞层和散布的中间神经元中最明显，尤其是在齿状回门区。GPER 1-IR在CA 3的所有层中均可见弥漫性表达，但在透明层中最密集。超微结构分析显示，离散核GPER 1-IR附属于质膜和内质网的神经元胞体和树突轴，突触的树突棘的专业化，和簇的小泡在轴突终末。此外，GPER 1-IR在无髓轴突和胶质细胞中也有表达。总体而言，GPER 1标记的配置文件的类型和数量在男性和女性之间是相似的，但是，在女性中，雌激素水平升高通常会增加轴突标记。在先前的研究中观察到的一些雌二醇诱导的变化被GPER激动剂G1复制：给药后6 h，G1增加卵巢切除小鼠CA 3的层oriens，lucidum和radiatum中的PSD 95-IR。相反，雌二醇而不是G1增加Akt磷酸化水平。相反，GPER 1在突触中的作用可能是由于与突触支架蛋白（如SAP 97）的相互作用。这些结果表明，尽管雌激素通过GPER 1的作用可能会集中在相同的突触元件上，但不同的通路用于实现这些作用。
Both estrous cycle and sex affect the numbers and types of neuronal and glial profiles containing the classical estrogen receptors α and β, and synaptic levels in the rodent dorsal hippocampus. Here, we examined whether the membrane estrogen receptor, G-protein-coupled estrogen receptor 1 (GPER1), is anatomically positioned in the dorsal hippocampus of mice to regulate synaptic plasticity. By light microscopy, GPER1-immunoreactivity (IR) was most noticeable in the pyramidal cell layer and interspersed interneurons, especially those in the hilus of the dentate gyrus. Diffuse GPER1-IR was found in all lamina but was most dense in stratum lucidum of CA3. Ultrastructural analysis revealed discrete extranuclear GPER1-IR affiliated with the plasma membrane and endoplasmic reticulum of neuronal perikarya and dendritic shafts, synaptic specializations in dendritic spines, and clusters of vesicles in axon terminals. Moreover, GPER1-IR was found in unmyelinated axons and glial profiles. Overall, the types and amounts of GPER1-labeled profiles were similar between males and females; however, in females elevated estrogen levels generally increased axonal labeling. Some estradiol-induced changes observed in previous studies were replicated by the GPER agonist G1: G1 increased PSD95-IR in strata oriens, lucidum, and radiatum of CA3 in ovariectomized mice 6 h after administration. In contrast, estradiol but not G1 increased Akt phosphorylation levels. Instead, GPER1 actions in the synapse may be due to interactions with synaptic scaffolding proteins, such as SAP97. These results suggest that although estrogen's actions via GPER1 may converge on the same synaptic elements, different pathways are used to achieve these actions.