OVARIAN STEROID REGULATION OF SEROTONIN NEURAL FUNCTION

卵巢类固醇对血清素神经功能的调节

• 批准号: 8173177
• 负责人: CYNTHIA Louise BETHEA
• 金额: $ 7.61万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173177
• 关键词: Arousal; Cells; Computer Retrieval of Information on Scientific Projects Database; DNA Fragmentation; DNA Repair; Dendrites; Dendritic Spines; Estrogens; Female; Fenfluramine; Funding; Gene Expression; Grant; In Situ Nick-End Labeling; Institution; Lasers; Macaca; Macaca mulatta; Moods; Neuronal Plasticity; Neurons; Neurophysiology - biologic function; Ovarian; Ovarian hormone; Progesterone; Prolactin; Regulation; Research; Research Personnel; Resources; Serotonin; Source; Steroids; TdT-Mediated dUTP Nick End Labeling Assay; United States National Institutes of Health; Vertebral column; cognitive function; dorsal raphe nucleus; improved; neurotransmission

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. We examined DNA fragmentation in serotonin neurons of the dorsal raphe nucleus with a TUNEL assay and found that E¿P treatment for one month significantly reduced TUNEL positive cells in ovarectomized female macaques. This indicates that ovarian steroids act on DNA repair mechanisms. Subsequently, we found that 64 probe sets related to DNA repair were increased by E¿P in laser-captured serotonin neurons. In addition, we determined the effect of ovarian steroid administration on gene expression related to dendritic spine protrusion in laser-captured serotonin neurons. We found that E¿P treatment for one month significantly increased expression of RhoA, Rac and cdc42 and their downstream effectors on a rhesus macaque microarray and confirmed these changes with qRT-PCR. These expression changes would increase spine proliferation on dendrites of serotonin neurons. Finally, we found that fenfluramine, a serotonin releaser that increases prolactin secretion, was less effective in macaques that were ovariectomized for 3 years compared to tubally ligated ovarian intact controls.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 该项目研究了雌激素（E）和孕酮（P）对猕猴中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元功能。预计5-羟色胺神经传递的升高有益于唤醒，提高情绪并改善认知功能。我们现在正在提出这样的假设，即卵巢恐怖还可以改善5-羟色胺神经外生和5-羟色胺神经元可塑性。我们使用TUNEL测定法检查了背侧raphe核的5-羟色胺神经元中的DNA片段化，发现一个月的E e处理可显着降低卵巢切除型雌性猕猴的TUNEL阳性细胞。这表明卵巢类固醇作用于DNA修复机制。随后，我们发现在激光捕获的5-羟色胺神经元中，E p增加了与DNA修复有关的64个探针集。此外，我们确定了卵巢类固醇给药对激光捕获的5-羟色胺神经元中与树突状脊柱蛋白相关的基因表达的影响。我们发现，一个月的e p处理显着增加了RhoA，RAC和CDC42的表达及其对恒河猕猴微阵列的下游影响，并证实了QRT-PCR的这些变化。这些表达变化会增加血清神经元树突上的脊柱增殖。最后，我们发现芬氟拉明是一种增加催乳素分泌的血清蛋白释放剂，与卵巢粘合的卵巢完整对照相比，在卵巢切除的猕猴中的有效性较低。