The program of research proposed is to investigate recovery of the C57BL/6 mouse from the parkinsonian condition induced by administration of the neurotoxin, MPTP. The work will test the hypothesis, formulated through preliminary research, that dopaminergic neurons spared from destruction by MPTP compensate for the loss of other dopaminergic neurons spared from destruction by MPTP compensate for the loss of other dopaminergic cells by increasing their own signaling functionality through axonal enlargement, production of new terminals, increased vesicle production in terminals, and synaptic division. Conventional EM over a time course of acute exposure to MPTP will produce evidence of compensation or, alternatively, of cellular replacement or repair of neurons in the substantial nigra and striatum. A repair that employs axon sprouting will be examined by counting over time immunohistochemically labeled dopaminergic cells This technique will also be used to identify as dopaminergic or not the neurons above, which densely vasiculated synaptic boutons. The site of action of MPTP and its derivatives will be investigated by identifying their precise subcellular locations within the nigral glial cells, neuronal cell bodies, and axons over time at the EM cells by autoradiography. The information provided by this project will result in a clearer understanding of the damage encountered in Parkinson's disease.
Showing the most recent 10 out of 47 publications
