Premium
Role of nitric oxide in rotenone‐induced nigro‐striatal injury
Author(s) -
He Yi,
Imam Syed Z.,
Dong Zaojun,
Jankovic Joseph,
Ali Syed F.,
Appel Stanley H.,
Le Weidong
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01938.x
Subject(s) - rotenone , substantia nigra , nitric oxide , tyrosine hydroxylase , nitric oxide synthase , chemistry , striatum , medicine , endocrinology , dopamine , nicotinamide adenine dinucleotide phosphate , pharmacology , biochemistry , mitochondrion , enzyme , oxidase test , dopaminergic
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.