AGING OF CENTRAL DOPAMINERGIC SYSTEMS IN PRIMATES

灵长类动物中枢多巴胺能系统的老化

• 批准号: 2871452
• 负责人: Don Marshall Gash
• 金额: $ 74.29万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-18 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2871452
• 关键词: aging; dopamine; psychomotor function

Increasing problems with rigidity, bradykinesia, tremor and gait disturbances are seen with advancing age. These movement dysfunctions are associated with a significant increase in morbidity and mortality in the elderly. Our studies in rhesus monkeys will initially focus on delineating the relationship between age-associated changes in the nigrostriatal system and the decline in motor functions during normal aging processes. Our research program project has been designed to critically test four hypotheses. Hypothesis 1: that rhesus monkeys undergo declines in motor functions which closely model those seen in humans. Hypothesis 2: that there is a gradual, continuous change in nigrostriatal dopaminergic function in rhesus monkeys with age. Hypothesis 3: that there is a gradual continuous loss of midbrain dopamine neurons in rhesus monkeys in aging. Hypothesis 4: that upregulation of the nigrostriatal dopaminergic system in older rhesus monkeys by intracerebral administrations of the potent dopaminergic trophic factor GDNF improve motor function. The program project is organized into three research projects which are supported by two core units. Project 1-3 are carefully integrated and coordinated to analyze motor functions and the nigrostriatal dopaminergic system in rhesus monkeys. An Administrative Core supports all three project, coordinating collection, pooling and analysis of data. A Primate Core Facility supervises and coordinates the use of all rhesus monkeys in these studies.

僵硬、运动迟缓、震颤和步态的问题越来越多 随着年龄的增长，会出现骚乱。这些运动 功能障碍与发病率的显著增加有关。 以及老年人的死亡率。我们对恒河猴的研究将会 最初的重点是描绘与年龄相关的 黑质纹状体系统的变化和运动功能的下降 在正常的老化过程中。我们的研究计划项目已经 旨在批判性地检验四个假说。假设1： 恒河猴运动功能下降，这与 模拟那些在人类身上看到的东西。假设2：有一个渐进的， 恒河猴黑质纹状体多巴胺能功能的动态变化 猴子随着年龄的增长。假设3：存在一个逐渐连续的 恒河猴衰老过程中中脑多巴胺能神经元的丢失。 假设4：黑质纹状体多巴胺能神经元的上调 脑内给药对老年恒河猴系统的影响 强效多巴胺能营养因子GDNF改善运动功能 功能。该计划项目被组织为三项研究 由两个核心单位支持的项目。项目1-3是 仔细整合和协调以分析运动功能和 恒河猴黑质纹状体多巴胺能系统。一个 管理核心支持所有三个项目，协调 数据的收集、汇集和分析。灵长类核心设施 监督和协调所有恒河猴在这些 学习。