Spatio-temporal distribution of reactive sulfur species during methylmercury exposure in the rat brain

Brain susceptibility to methylmercury (MeHg) is developmentally and regionally specific in both humans and rodents, but the mechanism is not well clarified. Reactive sulfur species (RSS) with high nucleophilicity can react with MeHg, leading to the formation of a less toxic metabolite bismethylmercury sulfide, thus exerting cytoprotection. In this study, we assessed the variation of RSS content in the rat brain and evaluated its relevance in sensitivity to MeHg. Analyses of fetal/juvenile rat brains showed low RSS levels in early developmental stages. Site-specific analysis of adult rat brains revealed that cerebellar RSS levels were lower than those of the hippocampus. Microscopically, RSS levels of the granular cell layer were lower than those of the molecular layer in the cerebellum. Thus, low RSS levels corresponded with age and site of the brain that is vulnerable to MeHg. Taken together with the finding that brain RSS were consumed during MeHg exposure, these results indicate that RSS is a factor that defines the specificity of MeHg vulnerability in the brain.