CATECHOLAMINERGIC NEURONS IN MAN: AGING AND DISEASE

脑儿茶酚胺(CA)神经元功能障碍已被认为是 神经和精神疾病(例如帕金森氏病， 阿尔茨海默氏症、老年性痴呆和精神分裂症)。CA神经元具有 与此类疾病相关的是中脑多巴胺(DA) 黑质和腹侧被盖区的神经元以及 蓝斑(LC)内含去甲肾上腺素(NE)神经元。在 人脑中，这些含CA细胞的数量随着年龄的增长而减少 尤其是帕金森氏症。这个项目的长期目标是 是确定CA细胞数量和/或受体的变化 属性与人类年龄和疾病相关的变化有关 行为。作为这一目标的初步准备，我们将首先收集规范性 关于(A)衰老、(B)偏侧性和(C)CA细胞的种族构成的数据 地形和感受器特性。第二，我们将检查帕金森症患者 以确定特定的疾病症状(例如，震颤， 僵直、动作迟钝、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、生化和 神经学，将在这个项目中使用。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进行识别 色素和CA合成酶酪氨酸羟基酶。这两个CA 原子核将被重建成一个三维空间，其中一个 最先进的计算机图形系统。生化上，~3H-螺环酮 纹状体和边缘/皮质DA区的结合将用于分析 突触后DA受体数目和敏感性。从神经学上讲， 帕金森氏症患者将在#年接受临床和定量评估 他们的特定疾病症状，以及他们的大脑 随后进行了解剖和生化检查，如上所述。这样的一种 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 它们伴随着衰老，为特定的神经基础提供了可能 帕金森氏病的症状，并为 儿茶酚胺相关疾病的未来研究。

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.