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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 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，即卵巢马还改善了5-羟色胺神经外生和5-羟色胺神经元可塑性。我们确定了卵巢类固醇给药对激光捕获的血清素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 e处理可显着增加RhoA，RAC和CDC42及其下游效应的基因表达。这些表达变化会增加血清神经元树突上的脊柱增殖。随后，我们将RhoA和Cdc42定位在大脑中的背侧Raphe区域。我们发现E+P显着增加了RhoA的细胞表达，并增加了Cdc42的树突状染色。我们还完成了对半猕猴的半猕猴的行为研究，这些猕猴已被卵巢切除或块茎结扎了3年。缺乏卵巢类固醇会降低5-羟色胺的产生，从而减少导航社交状况的成功和焦虑的行为，这些行为表现在孤立或压力的情况下。此外，我们完成了一项详尽的研究，对背侧raphe中CRF受体的CRF-UCN神经和表达。