Lead (Pb) exposure induces dopaminergic neurotoxicity in : Involvement of the dopamine transporter.

Lead (Pb) is an environmental neurotoxicant, and has been implicated in several neurological disorders of dopaminergic dysfunction; however, the molecular mechanism of its toxicity has yet to be fully understood. This study investigated the effect of Pb exposure on dopaminergic neurodegeneration and function, as well as expression level of several dopaminergic signaling genes in wild type (N2) and protein kinase C () mutant . Both N2 and mutant worms were exposed to Pb for 1 h. Thereafter, dopaminergic (DAergic) neurodegeneration, behavior and gene expression levels were assessed. The results revealed that Pb treatment affects dopaminergic cell morphology and structure in worms expressing green fluorescent protein (GFP) under a DAergic cell specific promoter. Also, there was a significant impairment in dopaminergic neuronal function as tested by basal slowing response (BSR) in wild-type, N2 worms, but no effect was observed in mutant worms. Furthermore, Pb exposure increased gene expression level when compared with N2 worms, but no alteration was observed in the mutant strains. LC-MS analysis revealed a significant decrease in dopamine content in worms treated with Pb when compared with controls. In summary, our results revealed that Pb exposure induced dopaminergic dysfunction in by altering gene levels, but mutants showed significant resistance to Pb toxicity. We conclude that PKC activation is directly involved in the neurotoxicity of Pb.