CATECHOLAMINERGIC NEURONS IN MAN: AGING AND DISEASE

脑中含有儿茶酚胺（CA）的神经元功能障碍与 神经和精神疾病（例如帕金森病， 老年痴呆症、老年痴呆症和老年痴呆症）。 CA神经元具有 与这些疾病有关的是中脑含多巴胺（DA）的 黑质和腹侧被盖区的神经元， 蓝斑（LC）的含去甲肾上腺素（NE）的神经元。 在 在人脑中，这些含CA的细胞随着年龄的增长而减少， 尤其是帕金森氏症。 本项目的长期目标 是确定CA细胞数量和/或受体的变化是否 在人类的年龄和疾病相关的变化涉及的属性 行为 为了实现这一目标，我们将首先收集规范 关于CA细胞的（a）老化、（B）偏侧性和（c）种族构成的数据 形貌和受体性质。 其次，我们将研究帕金森病 以确定特定的疾病症状（例如震颤， 强直、运动不能、痴呆）与局部CA细胞丢失相关。 一种多学科的方法，结合解剖学，生物化学和 神经病学，将用于该项目。 在解剖学上，中脑DA和 LC-NE神经元将根据其含有的神经黑色素来鉴定 色素和CA合成酶酪氨酸羟化酶。 这两个CA 原子核将被重建成一个三维空间， 最先进的电脑绘图系统 生物化学，3 H-螺哌隆 纹状体和边缘/皮质DA区域中的结合将用于测定 突触后DA受体数量和敏感性。 神经学上， 帕金森病患者将在临床上和定量评估， 他们的特定疾病的病理学，和他们的大脑 随后进行解剖学和生物化学检查，如上所述。 这样的 对人脑中这些核团的分析将阐明 这些细胞群的解剖特征，记录了地形变化 伴随着衰老，提供了一个可能的神经基础， 帕金森病的症状，并提供了一个规范的数据库， 未来的研究与儿茶酚胺有关的疾病。

Dysfunction of brain catecholamine (CA)-containing neurons has been linked to both neurologic and psychiatric disease (e.g. Parkinson's disease, Alzheimer's Senile Demewtia, and schizopnrenia). The CA neurons which have been related to such diseases are the midbrain dopamine (DA)-containing neurons of the substantia nigra and ventral tegmental area, and the norepinephrine (NE)-containing neurons of the locus coeruleus (LC). In the human brain, these CA-containing cells decrease in number with aging and especially so with Parkinson's disease. The long term goal of this project is to determine whether changes in CA cell number and/or receptor properties are involved in age- and disease-related changes in human behavior. As a preliminary to this goal, we will first gather normative data on (a) aging, (b) laterality, and (c) racial make-up of CA cell topographies and receptor properties. Second, we will examine parkinsonian brains to determine whether the particular disease symptoms (e.g. tremor, rigidity, akinesia, demential) are correlated with regional CA cell loss. A multidisciplinary approach, combining anatomy, biochemistry and neurology, will be used in this project. Anatomically, midbrain DA and LC-NE neurons will be identified in terms of their containing neuromelanin pigment and the CA synthesizing enzyme, tyrosine hydroxylase. These two CA nuclei will be reconstructed into a three-dimensional space with a state-of-the-art computer graphics system. Biochemically, 3H-spiperone binding in striatal and limbic/cortical DA regions will be used to assay postsynaptic DA receptor number and sensitivity. Neurologically, Parkinsonian patients will be clinically and quantitatively evaluated in terms of their specific disease symptomatology, and their brains subsequently examined anatomically and biochemically, as above. Such an analysis of these nuclei in the human brain will elucidate the basic anatomical features of these cell groups, document topographic changes which accompany aging, provide a possible neuronal basis for specific symptoms in Parkinson's disease, and provide a normative data-base for future research on catecholamine-implicated diseases.