Abstract
Abstract : Parkinson's disease (PD) is caused by deterioration of the dopamine (DA) nigrostriatal system. Loss of DA can be induced experimentally by neurotoxic lesion of DA neurotransmitter producing neurons in the substantia nigra, or through lesioning nigrostriatal DA terminations in the striatum with subsequent degeneration of their cell bodies in the substantia nigra. We have characterized a new animal model of preclinical PD. Experimental PD has been induced by unilateral, inranigral infusions of the neurotoxin malonate or 6-hydroxydopamine to produce partial loss of striatal DA. The animals were assessed weekly for forelimb use asymmetries to obtain a behavioral index of the striatal DA imbalance. The striata were examined morphologically and compared to the intact, contralateral side. Striatal DA terminal losses were determined by evaluation of expression of tyrosine hydroxylase. Differential changes in postsynaptic striatal DA receptor expression, and components of the intrinsic (mitochondrial) programmed cell death cascade occurred at 4 weeks after neurotoxin exposure. Effects of a secondary stress event on further exacerbation of striatal changes after the neurotoxin lesion are being examined. Neurochemical analysis of residual striatal DA following neurotoxin and secondary stressor exposure was performed in parallel, using HPLC of DA and its metabolites. Some tissues await evaluation,
Published Version
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