Nature Neuroscience
3, 1301 - 1306 (2000)
doi:10.1038/81834
Chronic systemic pesticide exposure reproduces features of Parkinson's diseaseRanjita Betarbet1, 2, Todd B. Sherer1, 2, Gillian MacKenzie1, Monica Garcia-Osuna1, Alexander V. Panov1
& J. Timothy Greenamyre11
Department of Neurology, Emory University, 1639 Pierce Drive, WMB 6000, Atlanta, Georgia 30322, USA
2
The first two authors contributed equally to this work
Correspondence should be addressed to J. Timothy Greenamyre jgreena@emory.eduThe cause of Parkinson's disease (PD) is unknown, but epidemiological studies suggest an association with pesticides and other environmental toxins, and biochemical studies implicate a systemic defect in mitochondrial complex I. We report that chronic, systemic inhibition of complex I by the lipophilic 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  -synuclein. These results indicate that chronic exposure to a common pesticide can reproduce the anatomical, neurochemical, behavioral and neuropathological features of PD.
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