Abstract
Rotenone, a widely used pesticide, causes a syndrome in rats that mimics, both behaviorally and pathologically, the symptoms of Parkinson's disease. The present study evaluated the role of nitric oxide in rotenone-induced nigro-striatal injury. After administration of rotenone in rats for 40 days, there was a moderate but significant injury of the nigro-striatal pathway indicated by a 47% decrease in striatal dopamine levels and a 28% loss of substantia nigra tyrosine hydroxylase-immunopositive neurons. Furthermore, a significant (37%) increase in the number of cells positive for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) in the striatum was observed, accompanied by a 83% increase in nitric oxide synthase (NOS) activity and a significant increase in the production of 3-nitrotyrosine (3-NT). There was a significant increase (45%) in the optical density of NADPH-d staining and an increase (72%) in NOS activity in the substantia nigra. Moreover, administration of the neuronal NOS inhibitor 7-nitroindazole significantly attenuated the increased NOS activity and 3-NT production, and provided significant protection against rotenone-induced nigro-striatal injury. Our data suggest that chronic rotenone administration can lead to significant injury to the nigro-striatal system, mediated by increased generation of nitric oxide.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Brain Chemistry
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Cell Count
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism
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Cerebral Cortex / pathology
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Corpus Striatum / drug effects
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Corpus Striatum / metabolism*
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Corpus Striatum / pathology
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Dopamine / metabolism
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Drug Administration Schedule
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Enzyme Inhibitors / pharmacology
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Female
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Indazoles / pharmacology
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Insecticides / toxicity
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NADPH Dehydrogenase / drug effects
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NADPH Dehydrogenase / metabolism
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Nerve Degeneration / chemically induced
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Nerve Degeneration / metabolism*
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Nerve Degeneration / pathology
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Neurons / drug effects
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Neurons / metabolism
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Neurons / pathology
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Nitric Oxide / metabolism*
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase Type I
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Peroxynitrous Acid / metabolism
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Rats
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Rats, Sprague-Dawley
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Rotenone / analysis
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Rotenone / blood
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Rotenone / toxicity*
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Signal Transduction / drug effects
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Substantia Nigra / drug effects
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Substantia Nigra / metabolism*
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Substantia Nigra / pathology
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Time
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Tyrosine 3-Monooxygenase / biosynthesis
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Uncoupling Agents / toxicity
Substances
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Enzyme Inhibitors
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Indazoles
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Insecticides
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Uncoupling Agents
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Rotenone
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Peroxynitrous Acid
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Nitric Oxide
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type I
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Nos1 protein, rat
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Tyrosine 3-Monooxygenase
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NADPH Dehydrogenase
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7-nitroindazole
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Dopamine