The aim of this project is to test the hypothesis that depletion of neurochemically specific neuronal groups in the intermediate reticular formation of the medulla is a substrate for autonomic and hypothalamic failure in patients with multiple system atrophy. Specifically, the project will involve quantitative analysis of neurons containing catecholamines, neuropeptide Y, substance P, and NADPH-diaphorase (a marker of nitric oxide producing neurons) in the ventrolateral medulla, the region of the nucleus of the tractus solitarius, and other structures of intermediate reticular zone in medullary tissue obtained at postmortem from patients evaluated at our institution for central autonomic failure, associated or not, with parkinsonism. We plan to use immunohistochemical staining for tyrosine hydroxylase, neuropeptide Y, and substance P, as well as histochemical staining for NADPH-diaphorase to study the medulla of four groups of age-matched patients: (1) patients with multiple system atrophy, (2) patients with idiopathic Parkinson's disease alone, (3) patients with parkinsonism and autonomic failure, and (54) controls with no neurologic disease. We plan to include a total of approximately 30-40 patients and study approximately 1-3 patients of each group (total 6-8 cases) per year. The results of the study will be important to increase our understanding on the pathophysiological mechanisms involving autonomic failure in multiple system atrophy nd to provide a basis for further research on diagnostic and therapy of this disorder.
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