Chapter B4 - Rotenone Rat and Other Neurotoxin Models of Parkinson Disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease marked by motor and non-motor abnormalities. The hallmark pathological features of PD are selective nigrostriatal dopaminergic degeneration and formation of filamentous, cytoplasmic inclusions called Lewy bodies. Brains of PD patients show evidence of extensive oxidative damage and microglial activation. The pathogenesis of idiopathic PD is believed to involve an interaction between genetic and environmental factors. Two recently developed animal models of PD investigate the involvement of environmental exposures in PD pathogenesis. In the rotenone model of PD, rats are exposed, chronically and systemically, to low dose of rotenone, a commonly used pesticide and specific mitochondrial complex I inhibitor. Thus, the rotenone and paraquat models of PD provide useful systems to understand PD pathogenesis and screen potential therapeutic strategies. The recently developed rotenone and paraquat models of PD provide novel systems to study mechanisms underlying the pathogenesis of the disease. Rats treated with rotenone demonstrate many features of PD including motor abnormalities, selective nigrostriatal dopaminergic degeneration, oxidative stress, microglial activation, a-synuclein aggregation, and selective reductions in proteasomal activity. Mice, chronically exposed to paraquat, demonstrate selective dopaminergic nigral cell loss, reactive gliosis, and formation of a-synuclein-positive inclusions. These models substantiate the involvement of pesticide exposures in PD. Future studies are required to evaluate therapeutic strategies for neuroprotection in these models of PD.