The overall objective of this project is to determine the role that oxidative stress plays in the dopaminergic neuropathology associated with Parkinson's disease (PD). The experimental animal model that will be used involves the 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal system in rodents. 6-OHDA lesions, and presumably PD, are, at least in part, oxidative stress-related phenomena mediated by free radicals. Thus, the administration of antioxidants should reduce the neuropathology resulting from 6-OHDA. Moreover, it is possible that neurotrophic factors have some antioxidant properties, so the administration of both therapeutic agents should be more effective than either compound alone. In addition, the behavioral and histological alterations resulting from 6-OHDA lesions of the STR in normal and hyperoxia-resistant rats will be examined. As 6-OHDA lesions are presumably mediated by free radicals, hyperoxia-resistant animals should be less affected by such a lesion than non-resistant control rats. These animals could therefore serve as a unique model system for the further study of oxidative stress-related neurodegenerative processes. In conclusion, this project should help to further our understanding of the mechanism of PD neuropathology and lead to novel therapeutic interventions.
