Abstract：
Neural-derived 17β-estradiol (E2) plays an important role in the synaptic plasticity of the hippocampus and prefrontal cortex, but the mechanism is not well defined. This study was designed to explore the effect and mechanism of neural-derived E2 on synaptic plasticity of the hippocampus and prefrontal cortex. Primary cultured hippocampal and prefrontal cells in mice were randomly divided into the DMSO (D), aromatase (Rate-limiting enzymes for E2 synthesizes) inhibitor letrozole (L), and ERs antagonist (MPG) treated groups. After intervention for 48 h, the cell was collected, and then, the expressions of AMPA-receptor subunit GluR1 (GluR1), synaptophysin (SYN), p-21-Activated kinase (PAK) phosphorylation, Rho kinase (ROCK), p-Cofilin, F-actin, and G-actin proteins were detected. Letrozole or ER antagonists inhibited the expression of GluR1, F-actin/G-actin, p-PAK and p-Cofilin proteins in prefrontal cells significantly. And the expressions of GluR1 and F-actin/G-actin proteins were declined in hippocampal cells markedly after adding letrozole or ERs antagonists. In conclusion, neural-derived E2 and ERs regulated the synaptic plasticity, possibly due to promoting actin polymerization in prefrontal and hippocampal cells. The regional specificity in the effect of neural-derived E2 and ERs on the actin polymerization-related pathway may provide a theoretical basis for the functional differences between the hippocampus and prefrontal cortex.
摘要：
神经源性17β-雌二醇（E2）在海马和前额叶皮层的突触可塑性中起重要作用，但是机制没有很好的定义。本研究旨在探讨神经源性E2对海马和前额叶皮层突触可塑性的影响及其机制。将原代培养的小鼠海马和前额叶细胞随机分为DMSO(D),芳香化酶（E2合成的限速酶）抑制剂来曲唑（L），和ERs拮抗剂(MPG)治疗组。干预48小时后，细胞被收集，然后,AMPA受体亚基GluR1(GluR1)的表达,突触素（SYN），p-21活化激酶（PAK）磷酸化，Rho激酶(ROCK),p-Cofilin,F-肌动蛋白,并检测到G-肌动蛋白蛋白。来曲唑或ER拮抗剂抑制GluR1，F-肌动蛋白/G-肌动蛋白的表达，p-PAK和p-Cofilin蛋白在前额叶细胞中表达显著。添加来曲唑或ERs拮抗剂后，海马细胞中GluR1和F-actin/G-actin蛋白的表达显着下降。总之,神经源性E2和ER调节突触可塑性，可能是由于促进前额叶和海马细胞的肌动蛋白聚合。神经源性E2和ERs对肌动蛋白聚合相关通路影响的区域特异性可能为海马和前额叶皮层的功能差异提供理论依据。
