Chronic systemic pesticide exposure reproduces features of Parkinson's disease.
The 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 alpha-synuclein. These results indicate that chronic exposure to a common pesticide can reproduce the anatomical, neurochemical, behavioral and neuropathological features of PD.
Betarbet
R
R
Department of Neurology, Emory University, 1639 Pierce Drive, WMB 6000, Atlanta, Georgia 30322, USA.
Sherer
T B
TB
MacKenzie
G
G
Garcia-Osuna
M
M
Panov
A V
AV
Greenamyre
J T
JT
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D020820:Dyskinesias / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D042967:Electron Transport Complex I; D004781:Environmental Exposure / Q000009:adverse effects*; D016631:Lewy Bodies / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000187:drug effects / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000633:toxicity*; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology
D012402:Rotenone; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; D004298:Dopamine