Methyl-mercury is an insidious organometallic cation that impairs neurological functions. Mercury interacts with cysteine thiolate groups and because these cysteine-methyl-mercury complexes mimic methionine, they may be transported across the blood brain barrier (BBB) and placenta via methionine transporters. Not only can these complexes freely move throughout the body, but they can inhibit the normal functions of heme proteins. Excess thiolate compounds may complex with free methyl-mercury and allow heme to remain unbound. Here, we examined the effect of a thiolate compound, meso-2,3-dimercaptosuccinic acid (DMSA), on the behavior of mice that received food containing methyl mercury (5.8 mg/kg) for a week during the day and night. Animals displayed unusual behavior after treatment with mercury. Administering DMSA (3 mg/kg) and α-lipoic acid (ALA; 3 mg/kg), which affects BBB transport, after methyl-mercury exposure significantly elevated daytime activity and restored night behavior by 40-60%. However, neither DMSA (3 mg/kg) nor L-cysteine (240 mg/kg) alone were as effective as both DMSA and ALA. These results suggest that when mercury interacts with cysteine thiolate groups on the surface of proteins in the brain and causes abnormal behavior, DMSA, with ALA, may reverse unusual behavior by eliminating bound mercury from proteins.
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