Paraquat induces selective dopaminergic nigrostriatal degeneration in aging C57BL/6 mice
Li, X.; Yin, J.; Cheng, C-mei.; Sun, J-lai.; Li, Z.; Wu, Y-liang.
Chinese Medical Journal 118(16): 1357-1361
2005
ISSN/ISBN: 0366-6999 PMID: 16157030 Document Number: 592407
Background: Paraquat (PQ; 1,1'-dimethyl-4,4'-bipyridinium), a widely used herbicide that is structurally similar to the known dopaminergic neurotoxicant MPTP (1-methyl-1,2,3,6-tetrahydropyridine), has been suggested as a potential etiologic factor for the development of Parkinson's disease (PD). Aging is an accepted risk factor for idiopathic Parkinson's disease. The aim of this study was to test the hypothesis that paraquat could induce PD-like nigrostriatal dopaminergic degeneration in aging C57BL/6 mice. Methods: Senile male C57BL/6 mice were intraperitoneally injected with either saline or PQ at 2-day intervals for a total of 10 doses. Locomotor activity and performance on the pole test were measured 7 days after the last injection and animals were sacrificed one day later. Level of dopamine (DA) and its metabolites levels in the striatum were measured by high-performance liquid chromatography with an electrochemical detector, and number of tyrosine hydroxylase [tyrosine 3-monooxygenase] (TH)-positive neurons was estimated using immunohistochemistry. Results: Locomotor activities were significantly decreased and the behavioural performance on the pole test were significantly impaired in the PQ-treated group. Levels of DA and its metabolites in the striatum were declined by 8 days after the last injection. Immunohistochemical analyses showed that PQ was associated with a reduction in number of TH-positive neurons. Conclusions: Long-term repeated exposures to PQ can selectively impair the nigrostriatal dopaminergic system of senile mice, suggesting that PQ could play an important role in the pathogenesis of PD. Our results also validate a novel model of PD induced by exposure to a toxic environmental agent.
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