AGE RELATED DECLINES IN MOVEMENT FUNCTIONS IN RHESUS MONKEYS

本修订计划项目补助金申请的项目2涉及 使用体内电化学的功能神经化学评估 记录技术、微透析方法和高性能 液相色谱-电化学检测 （HPLC-EC）研究多巴胺（DA）神经元系统中， 年轻成人（5 - 9岁）、成人（13 - 16岁）和 中年晚期/老年（20 - 24岁）恒河猴。 这个项目 将进行神经化学变化的功能研究， 衰老过程中的猴纹状体与行为， 组织学和免疫组织化学研究项目1和 项目3中的功能性MRI成像研究。第一，在体内 电化学和微透析方法将用于研究 钾诱发的DA溢出和p-酪胺诱发的 这些研究将在尾状核中进行。 核、壳核和丘脑核的三个年龄组的 猴子 除诱发DA释放外， 多巴胺和多巴胺代谢物将使用 微透析 其次，体内电化学和 微透析研究将用于研究功能性 多巴胺转运蛋白（DAT）位于 多巴胺能神经末梢 体内电化学方法将 用于观察DA摄取，并将使用微透析方法 研究GBR 12909和诺米芬新对 钾诱发的纹状体和核多巴胺释放 年轻和年老的猴子。 项目1还将 提供TH免疫反应神经元的组织学测量。 DAT的mRNA水平和含DA神经元的细胞计数 在年轻和年老的猴子的黑质中。 在 此外，项目1和3将与本项目合作， 调查年轻人和老年人的运动表现 动物为了确定是否有任何与年龄有关的变化， 运动行为和功能性MRI成像与变化相关 在DA的神经化学，最后，微透析措施， 基础水平的DA和钾诱发的DA溢出将是 在接受过 脑室内（ICV）注射媒介物或神经胶质衍生的 神经营养因子（GDNF）。 此外，DA摄取的研究将 在载体中使用体内电化学进行， GDNF处理的动物。 这些研究探讨了DA在以下方面的作用： 运动行为和内在的可塑性和补偿性 衰老多巴胺能神经元的神经化学特性 非人类灵长类动物

Project 2 of this revised program project grant application involves functional neurochemical assessments using in vivo electrochemical recording techniques, microdialysis methods and high performance liquid chromatography coupled with electrochemical detection (HPLC-EC) to study dopamine (DA) neuronal systems in the striatum of young adult (5-9 year old), adult (13-16 year old) and late middle-age/aged (20-24 year old) Rhesus monkeys. This project will perform functional studies of neurochemical changes to the monkey striatum during aging in conjunction with the behavioral, histological and immunohistochemical studies of Project 1 and functional MRI-imaging studies in Project 3. First, in vivo electrochemical and microdialysis methods will be used to investigate potassium-evoked overflow of DA and p-tyramine-induced displacement of DA. These studies will be carried out in the caudate nucleus, putamen, and nucleus accumbens of the three age groups of monkeys. In addition to the evoked released of DA, basal levels of dopamine and dopamine metabolites will be studied using microdialysis. Secondly, both in vivo electrochemical and microdialysis studies will be used to investigate the functional properties of the dopamine transporter (DAT) located on dopaminergic nerve terminals. In vivo electrochemical methods will be used to look at DA uptake and microdialysis methods will be used to investigate the effects of GBR12909 and nomifensine on potassium-evoked release of dopamine in the striatum and nucleus accumbens of the young and aging monkeys. Project 1 will also provide histological measures of TH immunoreactive neurons. mRNA levels of the DAT, and cell counts of DA-containing neurons in the substantia nigra of the young adult and aging monkeys. In addition, Projects 1 and 3 will collaborate with this project to investigate motoric performance in the young adult and aging animals. In order to determine whether any age-related changes in motoric behavior and functional MRI imaging correlate with changes in the neurochemistry of DA, Finally, microdialysis measures of basal levels of DA and potassium-evoked overflow of DA will be performed in middle-aged monkeys that have received intraventricular (ICV) injections of vehicle or glial-derived neurotrophic factor (GDNF). In addition, studies of DA uptake will be performed using in vivo electrochemistry in the vehicle and GDNF-treated animals. These studies address the role of DA in motor behavior and the inherent plasticity and compensatory neurochemical properties of aging dopaminergic neurons in nonhuman primates.