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: 8357731
• 负责人: CYNTHIA Louise BETHEA
• 金额: $ 5.82万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357731
• 关键词: Anxiety; Arousal; Behavior; Behavioral; Brain; Corticotropin-Releasing Hormone Receptors; Dendrites; Dendritic Spines; Dorsal; Estrogens; Funding; Gene Expression; Grant; Japanese Population; Lasers; Macaca; Moods; National Center for Research Resources; Neuronal Plasticity; Neurons; Neurophysiology - biologic function; Ovarian; Ovarian hormone; Primates; Principal Investigator; Progesterone; Regulation; Research; Research Infrastructure; Resources; Serotonin; Serotonin Production; Source; Staining method; Stains; Steroids; United States National Institutes of Health; Vertebral column; cognitive function; cost; improved; nerve supply; neurotransmission; social; success

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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 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 gene expression for RhoA, Rac and cdc42 and their downstream effectors. These expression changes would increase spine proliferation on dendrites of serotonin neurons. Subsequently, we localized RhoA and cdc42 to the dorsal raphe region in the brain. We found that E+P significantly increased the cellular expression of RhoA and increased the dendritic staining of cdc42. We also completed behavioral studies of semi-free ranging Japanese macaques that were ovariectomized or tubal ligated for 3 years. The lack of ovarian steroids reduced serotonin production resulting in less success in navigating social situations and in anxiety-like behaviors that are manifested in isolated or stressful situations. In addition, we finished an exhaustive study of the CRF-UCN innervation and expression of CRF receptors in the dorsal raphe.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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。我们确定了卵巢类固醇对激光捕获的5-羟色胺神经元中树突棘突出相关基因表达的影响。我们发现，E？P处理1个月后，RhoA、RAC和Cdc42及其下游效应物的基因表达显著增加。这些表达变化会增加5-羟色胺神经元树突上的棘突增殖。随后，我们将RhoA和CDC42定位到大脑的中缝背侧区域。我们发现E+P显著增加了RhoA的细胞表达，并增加了CDC42的树突状染色。我们还完成了半自由放养日本猕猴的行为学研究，这些猕猴被切除卵巢或结扎输卵管3年。卵巢类固醇的缺乏减少了5-羟色胺的产生，导致在社交场合中驾驭社交场合的成功率较低，以及在孤立或紧张的情况下表现出的类似焦虑的行为。此外，我们还对CRF-UCN神经支配和CRF受体在中缝背侧的表达进行了详尽的研究。