Chronic systemic pesticide exposure reproduces features of Parkinson's disease

The cause of Parkinson's disease (PD) is unknown, but epidemiological studi es suggest an association with pesticides and other environmental toxins, a nd biochemical studies implicate a systemic defect in mitochondrial complex I. We report that chronic, systemic inhibition of complex I by the lipophi lic pesticide, rotenone, causes highly selective nigrostriatal dopaminergic degeneration that is associated behaviorally with hypokinesia and rigidity . Nigral neurons in rotenone-treated rats accumulate fibrillar cytoplasmic inclusions that contain ubiquitin and alpha -synuclein. These results indic ate that chronic exposure to a common pesticide can reproduce the anatomica l, neurochemical, behavioral and neuropathological features of PD.