The primary aim of this project is to determine factors which promote survival and differentiation of adrenal medullary and other types of neuronal-like cells following grafting to the brain. Grafting will be studied using two rodent models of Parkinson's disease in which drug treatments have lesioned the dopaminergic nigrostriatal system. Growth and differentiation of grafted cells will be studied by a combination of neurochemical and morphological techniques including high performance liquid chromatography to measure catecholamine levels, and immunocytochemistry to study possible expression of monoaminergic and peptidergic neurotransmitter phenotypes. Using the 6-hydroxydopamine treated rat, the relationship between grafted cell differentiation and behavioral recovery will be studied. Using the MPTP (1-methyl-4-phenyl-1,2,5,6- tetrahydropyridine) treated mouse, effects of grafted cells on the recovery of damaged neurons in the host brain will be investigated. Conditions and techniques found to promote grafted cell survival and development, and behavioral or biochemical recovery in the host brain will extrapolated to primate studies in collaboration with co-investigators at the University of Rochester. These studies promise to be applicable to humans with damage to the central nervous system resulting from trauma, birth defects or neurodegenerative diseases, including Parkinson's disease.
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