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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Dopamine / metabolism
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Dyskinesias / etiology
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Dyskinesias / pathology
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Dyskinesias / physiopathology
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Electron Transport Complex I
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Environmental Exposure / adverse effects*
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Lewy Bodies / drug effects
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Lewy Bodies / metabolism
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Lewy Bodies / pathology
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Male
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NADH, NADPH Oxidoreductases / drug effects
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NADH, NADPH Oxidoreductases / metabolism
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Neostriatum / drug effects*
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Neostriatum / pathology
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Neostriatum / physiopathology
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Nerve Degeneration / chemically induced*
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Nerve Degeneration / pathology
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Nerve Degeneration / physiopathology
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Neural Pathways / drug effects*
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Neural Pathways / pathology
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Neural Pathways / physiopathology
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Neurons / drug effects
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Neurons / metabolism
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Neurons / pathology
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Parkinson Disease / pathology
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Parkinson Disease / physiopathology
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Parkinson Disease, Secondary / chemically induced*
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism
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Presynaptic Terminals / pathology
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Rats
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Rats, Inbred Lew
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Rats, Sprague-Dawley
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Rotenone / toxicity*
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Substantia Nigra / drug effects*
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Substantia Nigra / pathology
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Substantia Nigra / physiopathology
Substances
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Rotenone
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NADH, NADPH Oxidoreductases
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Electron Transport Complex I
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Dopamine