Role of nitric oxide in rotenone-induced nigro-striatal injury

Yi He, Syed Z. Imam, Zaojun Dong, Joseph Jankovic, Syed F. Ali, Stanley H. Appel, Weidong Le

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1338-1345
Number of pages8
JournalJournal of Neurochemistry
Volume86
Issue number6
DOIs
StatePublished - Sep 2003

Keywords

  • Dopamipe
  • Nigro-striatum
  • Nitric oxide
  • Parkinson's disease
  • Rotenone

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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