NOREPINEPHRINE IN STRESS-INDUCED AMENORRHEA OF MACAQUES

去甲肾上腺素在压力引起的猕猴闭经中的作用

• 批准号: 8357842
• 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/8357842
• 关键词: Amenorrhea; Animals; Anxiety Disorders; Brain Stem; Cell Nucleus; Chronic; Diet; Female; Fiber; Functional disorder; Funding; Gene Proteins; Grant; Lead; Life Stress; Macaca; Moderate Exercise; Monkeys; National Center for Research Resources; Neuraxis; Neurons; Norepinephrine; Pharmaceutical Preparations; Physiological; Pilot Projects; Play; Primates; Principal Investigator; Psychological Stress; Research; Research Infrastructure; Resistance; Resources; Role; Serotonin; Source; Stress; Testing; United States National Institutes of Health; cost; density; nerve supply; norepinephrine system; prevent; reboxetine; reproductive; reproductive axis

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 is a new project to determine whether the brain stem norepinephrine (NE) system plays a role in the mechanisms by which common life stresses (i.e., dieting, moderate exercise and psychological stress) impair activity of the reproductive axis. We have substantial evidence that stress sensitive (SS) females have lower serotonergic function in the central nervous system. Moreover, serotonin inhibits the NE neurons of the locus ceruleus (LC) nucleus in the brain stem. This means that the reduction in serotonin in the SS animals may lead to chronic over-activation of NE neurons in the LC, and over-activation of these neurons has been implicated in anxiety disorders. Therefore, we will test the hypothesis that elevated activity of the NE system in the LC is responsible for the suppression of the reproductive axis in stress-sensitive monkeys. Aim 1 will conduct pilot studies to determine the physiological function of the NE system in SS and stress resilient (SR) monkeys and to determine if the antianxiety medication, reboxetine, will prevent stress-induced reproductive dysfunction (subcontracted to Dr. Judy Cameron, Univ Pittsburgh). Aim 2 will determine the expression of pivotal genes and proteins in the NE neurons of the LC and examine the fiber density of stress-related afferent innervation of the LC in SS, plus moderately and highly SR monkeys in the presence and absence of stress. Analysis of the locus ceruleus of stress-resistant and stress sensitive animals euthanized in the presence and absence of stress is underway.

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。 这是一个新的项目，旨在确定脑干去甲肾上腺素(NE)系统是否在常见的生活压力(即节食、适度运动和心理压力)损害生殖轴活动的机制中发挥作用。我们有大量证据表明，应激敏感(SS)女性中枢神经系统的5-羟色胺能功能较低。此外，5-羟色胺还抑制脑干蓝斑(LC)核的去甲肾上腺素神经元。这意味着SS动物体内5-羟色胺的减少可能导致LC中NE神经元的慢性过度激活，而这些神经元的过度激活可能与焦虑障碍有关。因此，我们将检验这一假设，即LC中NE系统的活性升高是应激敏感猴子生殖轴受到抑制的原因。Aim 1将进行试点研究，以确定SS和压力弹性(SR)猴子的NE系统的生理功能，并确定抗焦虑药物瑞波西汀是否可以防止压力导致的生殖功能障碍(转包给匹兹堡大学的朱迪·卡梅隆博士)。目的2研究在有无应激的情况下，SS+中、高度SR猴LC内NE神经元关键基因和蛋白的表达，以及LC应激相关传入神经纤维密度的变化。对在有无应激情况下实施安乐死的耐应激和应激敏感动物蓝斑的分析正在进行中。