Membrane-Initiated Estradiol Signaling Induces Spinogenesis Required for Female Sexual Receptivity
Membrane-Initiated Estradiol Signaling Induces Spinogenesis Required for Female Sexual Receptivity
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DOI：
10.1523/jneurosci.3030-11.2011
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发表时间：
2011-11-30
影响因子：
5.3
通讯作者：
Micevych, Paul
中科院分区：
文献类型：
--
作者：
Christensen, Amy;Dewing, Phoebe;Micevych, Paul
雌激素在发育和成年期对神经系统的结构有深远的作用。雌二醇的标志性作用之一是改变神经过程的形态。在海马体中，雌二醇调节影响认知行为的棘和细胞兴奋性。在下丘脑，雌二醇增加调节生殖的下丘脑内侧基底核的棘密度。下丘脑弓状核（ARH）是调节雌性性感受性的重要部位，其树突棘密度具有性别二型性，有利于雌性。在本研究中，我们同时使用β-肌动蛋白免疫染色和高尔基体染色来观察雌二醇诱导的Long-Evans大鼠脊柱密度的变化。高尔基体浸渍用于可视化棘形状，然后β-肌动蛋白免疫反应性被用作棘可塑性的半定量测量，因为肌动蛋白形成树突棘的核心。雌二醇处理后4 h，β-肌动蛋白免疫荧光和丝状伪足棘均增加（从70.57 ± 1.09%增加到78.01 ± 1.05%，p < 0.05）。用细胞松弛素D破坏雌二醇诱导的β-肌动蛋白聚合减弱了脊柱前凸行为，表明雌二醇介导的棘发生对雌性性感受性的重要性（81.43 +/- 7.05至35.00 +/- 11.76，p < 0.05）。肌动蛋白解聚因子cofilin的失活是脊髓发生所必需的。膜启动的雌二醇信号涉及代谢型谷氨酸受体1a负责磷酸化，从而失活的cofilin。这些数据表明，雌二醇诱导的ARH的棘发生是一个重要的细胞机制，为女性性行为的调节。
Estrogens have profound actions on the structure of the nervous system during development and in adulthood. One of the signature actions of estradiol is to alter the morphology of neural processes. In the hippocampus, estradiol modulates spines and cellular excitability that affect cognitive behaviors. In the hypothalamus, estradiol increases spine density in mediobasal hypothalamic nuclei that regulate reproduction. The hypothalamic arcuate nucleus (ARH), an important site for modulation of female sexual receptivity, has a sexual dimorphism in dendritic spine density that favors females. In the present study, we used both beta-actin immunostaining and Golgi staining to visualize estradiol-induced changes in spine density in Long-Evans rats. Golgi impregnation was used to visualize spine shape, and then beta-actin immunoreactivity was used as a semiquantitative measure of spine plasticity since actin forms the core of dendritic spines. At 4 h after estradiol treatment, both beta-actin immunofluorescence and filopodial spines were increased (from 70.57 +/- 1.09% to 78.01 +/- 1.05%, p < 0.05). Disruption of estradiol-induced beta-actin polymerization with cytochalasin D attenuated lordosis behavior, indicating the importance of estradiol-mediated spinogenesis for female sexual receptivity (81.43 +/- 7.05 to 35.00 +/- 11.76, p < 0.05). Deactivation of cofilin, an actin depolymerizing factor is required for spinogenesis. Membrane-initiated estradiol signaling involving the metabotropic glutamate receptor 1a was responsible for the phosphorylation and thereby deactivation of cofilin. These data demonstrate that estradiol-induced spinogenesis in the ARH is an important cellular mechanism for the regulation of female sexual behavior.