Characterization of methylmercury demethylation in the central nervous system.

The toxicity of mercury is dependent on its chemical composition at its point of entry and site of toxicity. Differences in toxicity indicate that inorganic mercury (iHg) and methylmercury (MeHg) mediate adverse reactions via different mechanisms. Based on the available toxicity data, demethylation of MeHg to iHg has proven detrimental as it increases the severity of toxic insult. Accordingly, an in vitro system was established in order to characterize the demethylation reaction using primary astrocytes from neonatal rat cerebellum. Incubation of MeHg with a pro-oxidant increased the rate of demethylation (control vs. rotenone = -1.86±5.57 vs. 16.27±2.68%, p<0.05) and accumulation (control vs. rotenone = 86.53±4.13ng/mg vs. 23.6±3.80ng/mg, p<0.001) relative to control. These findings suggest that demethylation is not only harmful as a result of increased iHg levels, but also because total mercury is increased. In light of rising atmospheric mercury levels, it is important that this pathway be fully characterized.