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: 6349726
• 负责人: Don Marshall Gash
• 金额: $ 74.1万
• 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/6349726
• 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.

增加僵化，颤音，震颤和步态的问题 随着年龄的增长，人们可以看到骚乱。 这些运动 功能障碍与发病率显着增加有关 和老年人的死亡率。 我们在恒河猴的研究将 最初专注于描述与年龄相关的关系 黑质系统的变化和运动功能的下降 在正常老化过程中。 我们的研究计划项目有 被设计为批判性检验四个假设。 假设1：那 恒河猴的运动功能下降 建模那些在人类中看到的人。 假设2：有一个逐渐的 恒河猴的长纹状体多巴胺能功能的持续变化 随着年龄的增长。 假设3：有一个逐渐连续的 衰老中恒河猴中脑多巴胺神经元的丧失。 假设4：斑纹乳清多巴胺能的上调 旧恒河猴的系统由脑内管理 有效的多巴胺能营养因子GDNF改善电动机 功能。 该计划项目分为三项研究 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，并且 恒河猴的黑质多巴胺能系统。 一个 行政核心支持这三个项目，协调 收集，汇总和分析数据。 灵长类动物核心设施 监督和协调在这些中使用所有恒河猴的使用 研究。