Participation of N-methyl-d-aspartate receptors on methylmercury-induced DNA damage in rat frontal cortex

Methylmercury (MeHg) inhibits glutamate uptake by astrocytes, which can contribute to neuronal loss through excitotoxicity. We explored the extent at which this phenomenon is involved in MeHg-induced DNA damage in the rat cortex. MeHg amounts that increase extracellular glutamate (1.5, 7.5 and 15 nmol, according to previous reports) were stereotaxically injected in the frontal cortex of adult rats before DNA-damage determination by means of a quantitative TUNEL assay. After either 24 or 48 h, the cortex of all exposed animals showed significant increments of damaged DNA, compared with rats that only received sterile saline. In parallel experiments, we found that the administration of a non competitive NMDA receptor antagonist (MK-801, 10 mg/kg, i.p.) 1 h before MeHg injection, significantly reduced DNA damage. These results demonstrate that activation of NMDA receptors contributes importantly to MeHg neurotoxicity.