title: Chronic systemic pesticide exposure reproduces features of Parkinson's disease.
abstract: 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.
authors: Department of Neurology, Emory University, 1639 Pierce Drive, WMB 6000, Atlanta, Georgia 30322, USA.
authors: R
authors: R
authors: Betarbet
authors: T B
authors: TB
authors: Sherer
authors: G
authors: G
authors: MacKenzie
authors: M
authors: M
authors: Garcia-Osuna
authors: A V
authors: AV
authors: Panov
authors: J T
authors: JT
authors: Greenamyre
mesh_terms: 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
chemical_list: D012402:Rotenone; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; D004298:Dopamine