GROWTH AND AGING--ANATOMY OF SUBSTANTIA NIGRA

生长与衰老--黑质的解剖

• 批准号: 3476751
• 负责人: Gay R Holstein
• 金额: $ 8.54万
• 依托单位: MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-08-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3476751
• 关键词: Macaca mulatta; aging; animal old age; biological models; brain cell; cell death; dendrites; dopamine; electron microscopy; enkephalins; gamma aminobutyrate; histochemistry /cytochemistry; immunochemistry; immunocytochemistry; infant animal; mature animal; microscopy; neuroanatomy; neurogenesis; neurons; neuropil; neurotransmitters; newborn animals; serotonin; statistics /biometry; substance P; substantia nigra; synapses

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.

拟议研究的目标是系统研究 形态学和免疫细胞化学的变化，发生在 灵长类大脑的生长发育和衰老 模型 选择进行研究的是恒河猴的黑质（SN）。 该项目的具体目标是（1）确定 在形态学上明显的质的变化， 黑质神经元从出生到衰老，（2）量化 黑质神经元的数量存在于这个核和 在生命的每个阶段的核体积，（3）表征 发育期、成年期和 老年猴SN，（4）以量化这些超微结构变化 使用适当的统计数学分析，以及（5） 免疫细胞化学定位、表征和量化- 确定了神经元、树突和 在每个发展和老化阶段的终端。 这些目标 将在光镜（LM）和电子显微镜下完成 (EM)水平，使用广泛的技术，包括经典的 LM的Golgi和Nissl方法，LM-EM的Golgi-gold调色法 相关性，定量分析，包括超微结构 体视学，定性和定量后包埋，以及 作为单标记和双标记包埋前免疫细胞化学。 所有这些研究将分别对来自 网状部（SNr）。 拟议的研究旨在产生关于 猴子黑质的形态学自然史。 自然和时间提供了一个强有力的独立变量， 以这样一种方式运作，即老化代表一个连续体，或 逆转，是发展的特征。 这 研究是理解结果的第一步 侵入性的实验操作，以及干扰 正常发育和衰老， 环境和代谢紊乱。 因此， 这项调查将为解释 行为和临床研究的正常和实验- 运动系统发育改变，运动障碍研究 黑质纹状体通路，缺陷，脑移植研究 包括胚胎黑质组织的植入，以及行为，临床 以及正常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、莱-尼二氏综合征、抽动秽语综合征 综合征和迟发性运动障碍都被怀疑 包括黑质功能障碍