Rotenone neurotoxicity: Relevance to Parkinson's disease

Rotenone is one of the most widely used insecticide and pisicides in the US and around the world. Epidemiological evidences suggest that rotenone exposure may be a risk factor for Parkinson's disease (PD) pathogenesis. Numerous experimental studies prompted such epidemiological studies showing that rotenone produces a PD phenotype in animal models. Various laboratory animals exposed to rotenone exhibit a loss of dopaminergic neurons and specific protein aggregate formation consistent with the major pathological hallmarks of PD. Mechanistic research has shown that inhibition of complex I of the mitochondrial electron transport chain is the primary mechanism of neurotoxic action. Some studies have pointed to other mechanisms such as disruption of microtubule function. Systemic exposure in rats below doses that affect Adenosine triphosphate (ATP) production is the most commonly used rotenone PD model. Here, rotenone enters all cells but selectively affects dopaminergic neurons in the substantia nigra due to high sensitivity to oxidative insults. This chapter briefly covers the history of rotenone neurotoxicity studies, its neurotoxic mechanisms and several related experimental models demonstrating the neurochemical, histopathological and behavioral characteristics identical to clinical PD.