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 substantial loss of dopamine neurons from the substantia nigra, decreased dopamine function assessed biochemically, and the classical signs of tremor, motor inhibition, muscular rigidity, incoordination and behavioral impairment. This syndrome resulting from MPTP may provide clues to the cause of """"""""idiopathic"""""""" Parkinson's disease or other age-related changes in dopamine systems as well as a means to study treatment strategies. The replacement of dopamine function with transplanted fetal neurons is one approach, supported by numerous recent studies in non-primate species and by our own data in African green monkeys demonstrating feasibility. This program proposes, therefore, to study the development of fetal dopamine systems, to characterize the acute and long-term effects of MPTP on neuronal morphology, dopamine biochemistry, and behavior, and to study the effects of fetal neuron transplantation on these processes during various time periods in monkeys. Morphological evidence of neuronal survival, biochemical confirmation of dopamine production and regulation, and functional improvement in parkinsonian signs and behaviors over long time periods in a primate species is essential as the next step in consideration of possible human therapeutic approaches. These studies may also lead to improved understanding of the plasticity and function of dopamine neurons and systems.
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