Selective vulnerability of the striatal subregions of C57BL/6 mice to paraquat

Abstract

Paraquat (PQ) is a strong redox agent that contributes to the formation of reactive oxygen species (ROS) and induces toxicity of the nigrostriatal dopaminergic system. In this study, we investigated the effect of PQ on the dopaminergic system of four striatal subregions. Male C57BL/6 mice (aged 7 weeks and 23-25 g) were used for this study. The mice were administrated with normal saline or PQ (10mg/kg i.p.) twice weekly for three consecutive weeks, and we evaluated changes in body weight and the performance of motor coordination. We also measured changes in tyrosine hydroxylase (TH) immunoreactivity, dopamine (DA) and its metabolites, reduced glutathione (GSH), and oxidized glutathione (GSSG) in the striatum. The body weight gain of PQ-treated mice was lower than that of control mice 2 weeks after PQ administration, and this lowering effect was sustained until 4 weeks after PQ administration. In the rota-rod test, PQ had a significant effect on the time it took mice to fall from the rotating rod at 2 weeks after injection as compared to the control rats, and the effect was sustained up to 4 weeks after PQ administration. Additionally, the densities of TH-positive fibers were reduced in dorsal regions of both the striata and ventral subregion of the caudal striatum (RD, CD and CV subregions). The DA level however, decreased in four subregions of the striata. The rate of DA oxidation and O-methylation increased in the RD subregion. After PQ administration, GSH levels were significantly reduced in the RD and CV subregions, but GSSG levels in the RD and CD subregions increased compared to the control rats. The ratio of GSH/GSSG also decreased in the RD and CD subregions. We found that repeated PQ injection altered DA metabolism through the generation of oxidative stress in the striatum, and although the RD subregion showed the most prominent change, the dorsal region of the striatum may be more sensitive to PQ exposure.