Paraquat induces selective dopaminergic nigrostriatal degeneration in aging C57BL/6 mice.
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 (HPLC-ECD), and numbers of tyrosine hydroxylase (TH) positive neurons were estimated using immunohistochemistry.


RESULTS
Locomotor activities were significantly decreased and the behavioral performance on the pole test were significantly impaired in the PQ treated group. Level of DA and its metabolites levels in the striatum were declined by 8 days after the last injection. Immunohistochemical analyses showed that PQ was associated with a reduction in numbers of tyrosine hydroxylase positive neurons.


CONCLUSIONS
Long-term repeated exposes to PQ can selectively impair the nigrostriatal dopaminergic system of senile mice, suggesting that PQ could play an important role in the pathogenesis of Parkinson's disease (PD). Our results also validate a novel model of PD induced by exposure to a toxic environmental agent.
Li
Xia
X
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.
Yin
Jun
J
Cheng
Chun-mei
CM
Sun
Jin-lai
JL
Li
Zheng
Z
Wu
Ying-liang
YL
D000375:Aging / Q000473:pathology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D010269:Paraquat / Q000633:toxicity*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D013378:Substantia Nigra / Q000187:drug effects* / Q000201:enzymology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D014446:Tyrosine 3-Monooxygenase; D010269:Paraquat; D004298:Dopamine