Degenerative Risks for Parkinson's Disease After Toxin Exposure and Stress
Annual rept. 1 Jul 2001-30 Jun 2002
FINCH UNIV OF HEALTH SCIENCES/CHICAGO MEDICAL SCHOOL IL
Pagination or Media Count:
Parkinsons disease PD is caused by deterioration of the dopamine DA nigrostriatal system. Loss of DA can be induced experimentally by neurotoxin lesion of DA neurotransmitter producing neurons in the substantia nigra, or through lesioning DA axon terminals in the striatum with subsequent degeneration of their cell bodies in the substantia nigra. We have produced and characterized a new animal model of preclinical PD. Experimental PD has been induced by unilateral, intranigral infusions of the neurotoxin malonate to produce partial loss of nigrostriatal DA. The animals were assessed weekly for forelimb asymmetries for 4 weeks to obtain a behavioral index of the subtotal DA loss. The striata were examined morphologically and compared to the intact, contralateral side. Presynaptic striatal DA terminal losses were determined by evaluation of expression of tyrosine hydroxylase. Differential changes in postsynaptic striatal DA receptor expression and cleaved caspase-3 occurred at 4 weeks after neurotoxin exposure. Subsequent experiments examined effects of a secondary stressor on further exacerbation of striatal changes following the neurotoxin lesion. 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 are awaiting evaluation.
- Medicine and Medical Research