Degenerative Risks for Parkinson's Disease After Toxin Exposure and Stress
Abstract
Parkinson's 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA416993
Entities
People
- Marjorie A. Ariano
Organizations
- Rosalind Franklin University of Medicine and Science