MPTP (1-methyl 4-phenyl 1,2,5,6-tetrahydropyridine) produces behavioral changes in human and non-human primates which closely resemble Parkinson's disease. The morphological, biochemical, and behavioral alterations it produces are long-lasting. They include loss of dopamine neurons from the substantia nigra, decreased dopamine function assessed biochemically, and classical parkinsonian signs of tremor, motor inhibition, muscular rigidity, incoordination and behavioral impairment. This MPTP-induced syndrome provides a useful model for studying the functional, biochemical, and morphological sequellae of the transplantation of fetal mesencephalic tissue containing dopamine neurons. In the initial phases of this program we have demonstrated that fetal substantia nigra tissue, transplanted into the caudate nucleus of MPTP-treated monkeys, will survive, grow, extend axons, improve dopamine levels, and restore near-normal motor and behavioral function for up to 7.5 months. This program proposes, therefore, to continue studies of the following: (1) the effects of fetal neural transplantation on neuronal morphology, dopamine biochemistry, and behavior during longer time periods in monkeys: (2) to examine the function of these grafts and their integration with the host, using morphological, electron microscopic, biochemical and pharmacological techniques, and behavioral methods: (3) to characterize the acute and long-term effects of MPTP and compared them with the neural alterations found in Parkinson's disease: (4) to study the development of fetal dopamine systems in the African green monkey and examine new methods which might further improve techniques for neural transplantation in primates. These studies may lead to improved understanding of the plasticity and function of dopamine systems and human diseases associated with alterations in dopamine function.
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