OVARIAN STEROID REGULATION OF SEROTONIN NEURAL FUNCTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本项目研究雌激素(E)和孕酮(P)对猕猴5-羟色胺神经功能的影响。5-羟色胺控制着许多自主神经和高阶神经功能。5-羟色胺神经传递的增加有望有助于唤醒、提升情绪和改善认知功能。我们现在正在寻求一种假设，即卵巢激素也可以提高5-羟色胺神经元的存活率和5-羟色胺神经元的可塑性。神经可塑性通过神经系统的一系列结构变化表现出来，但在中枢神经系统中，树突棘是神经元可塑性的基本结构单位。树突棘只表达兴奋性谷氨酸突触，从而增加对相应神经元的刺激性输入。树突棘以一种明确的方式突出，涉及Rho GTP酶、RhoA、rac1和CDC42。Rho GTP酶控制肌动蛋白的聚合、分支和捆绑，使它们能够调节肌动蛋白细胞骨架的重塑，形成不同的结构元素。我们研究了卵巢类固醇对激光捕获的5-羟色胺神经元中Rho GTP酶及其下游信号通路成员基因表达的影响。去势(手术绝经)雌性恒河猴给予安慰剂、雌激素(E)或雌激素+孕酮(E+P)治疗1个月(n=3/组)。取中脑7h切片，进行色氨酸羟化酶(TPH)免疫组织化学染色，用Arcturus激光捕获显微镜PixCell II捕捉已鉴定的神经元。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project examines the effect of estrogen (E) and progesterone (P) on serotonin neural function in macaques. Serotonin governs many autonomic and higher order neural functions. An elevation in serotonin neurotransmission is expected to benefit arousal, elevate mood and improve cognitive function. We are now pursing the hypothesis that ovarian hormones also improve serotonin neuron survival and serotonin neuronal plasticity. Neuroplasticity is manifested through a number of structural changes in the nervous system, but in the CNS, dendritic spines are the elementary structural units of neuronal plasticity. Dendritic spines exclusively express excitatory glutamate synapses and thereby increase stimulatory input to the respective neuron. Dendritic spines are protruded in a well-defined manner that involves the Rho GTPases, RhoA, Rac1 and cdc42. Rho GTPases control the polymerization, branching and bundling of actin, allowing them to regulate the remodeling of the actin cytoskeleton into distinct architectural elements. We determined the effect of ovarian steroid administration on gene expression of the Rho GTPases and members of their downstream signaling pathways in laser captured serotonin neurons. Ovariectomized (surgically menopausal) female rhesus monkeys were administered placebo, estrogen (E) or estrogen plus progesterone (E+P) for one month (n=3/group). The midbrain was sectioned at 7 ¿, immunostained for tryptophan hydroxylase (TPH) and identified neurons were captured using an Arcturus Laser Capture Microscope PixCell II.