GROWTH AND AGING--ANATOMY OF SUBSTANTIA NIGRA

拟议研究的目标是系统地研究 细胞形态和免疫细胞化学的变化 灵长类动物大脑的生长、发育和衰老。模型 研究对象为恒河猴的黑质(SN)。 该项目的具体目标是：(1)确定 在形态上明显的质变 黑质神经元从出生到衰老，(2)定量 黑质神经元的数量和黑质神经元的数量 生命每个阶段的细胞核体积，(3)表征 发育、成虫和幼虫的信号超微结构特征 老年猴SN，(4)对这些超微结构的变化进行量化 使用适当的统计数学分析和(5) 对免疫细胞化学进行定位、表征和量化- 已确定的神经递质对神经元、树突和 终端处于发育和老化的各个阶段。这些目标 将在光(LM)和电子显微镜下完成 (Em)水平，使用广泛的技术，包括经典 Lm的Golgi和Nissl方法，Lm-EM的Golgi-Gold色调 相关性、包括超微结构在内的定量分析 体视学、定性和定量植入后 单标和双标包埋前免疫细胞化学。 所有这些研究都将分别在以下材料上进行 致密部(SNC)和网状部(SNR)。 拟议的研究旨在产生关于以下方面的规范数据 猕猴黑质的形态自然史。 自然和时间提供了一个强有力的自变量，它可能 以这样一种方式运行，即老化代表一个连续体，或一个 反转，这些事件是发展的特征。这 研究是理解研究结果的第一步 侵入性的实验操作以及干扰 由于创伤导致的正常发育和衰老， 环境和新陈代谢紊乱。因此，结果是 这项调查将为解释 正常人和实验者的行为和临床研究 运动系统发育改变，运动障碍的研究 黑质纹状体通路，缺陷，脑移植研究 涉及胎儿黑质组织的植入，以及行为和临床 以及正常衰老和异常衰老的药理学研究 流程。帕金森氏症，亨廷顿氏症， 精神分裂症、Lesch-Nyhan综合征、抽动症 综合征和迟发性运动障碍都被怀疑是 包括黑质功能障碍。

The objective of the proposed research is the systematic study of morphologic and immunocytochemical changes which occur during growth, development and aging in primate brain. The model chosen for study is the substantia nigra (SN) of rhesus monkeys. The specific aims of the project are (1) to determine the qualitative changes which are apparent in the morphology of substantia nigra neurons from birth to senescence, (2) to quantify the number of nigral neurons present in this nucleus and the volume of the nucleus at each stage of life, (3) to characterize the signal ultrastructural features of developmental, adult and aged monkey SN, (4) to quantify these ultrastructural changes using an appropriate statistico-mathematical analysis and (5) to localize, characterize and quantify the immunocytochemically- identified neurotransmitter endowment of neurons, dendrites and terminals at each stage of development and aging. These aims will be accomplished at the light (LM) and electron microscopic (EM) levels, using a wide range of techniques including the classic Golgi and Nissl methods for LM, Golgi-gold toning for LM-EM correlations, quantitative analysis including ultrastructural stereology, qualitative and quantitative post-embedding, as well as single and double label pre-embedding immunocytochemistry. All of these studies will be conducted separately on material from pars compacta (SNc) and pars reticulata (SNr). The proposed studies are designed to yield normative data on the morphologic natural history of the monkey substantia nigra. Nature and time provide a potent independent variable which may operate in such a fashion that aging represents a continuum, or a reversal, of the events which characterize development. This research constitutes a first step toward understanding the results of invasive experimental manipulations, as well as interferences with normal development and aging due to traumatic, environmental and metabolic disturbances. As such, the results of this investigation will provide a basis for the interpretation of behavioral and clinical studies of normal and experimentally- altered motor system development, studies of movement disorders and nigrostriatal pathways, deficits, brain transplant studies involving implants of fetal nigral tissue, and behavioral, clinical and pharmacologic studies of normal and abnormal aging processes. Parkinson's disease, Huntington's disease, schizophrenia, the Lesch-Nyhan syndrome, Gilles de la Tourette syndrome and tardive dyskinesia have all been suspected to encompass dysfunction of the substantia nigra.