Abstract
The effects of methylcobalamin and cyanocobalamin, vitamin B_<12> analogs, on glutamate-induced neuronal death were examined using cortical cultures. Cell viability was markedly reduced by a brief exposure to glutamate followed by 1-hour incubation with glutamate-free medium. Glutamate-induced neurotoxicity was prevented by MK-801, an antagonist of N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Glutamate neurotoxicity was inhibited by removing extracellular Ca^<2+> during glutamate exposure. Glutamate neurotoxicity was also inhibited by N^ω-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, and hemoglobin, which traps NO. NO donors such as sodium nitroprusside induced neurotoxicity with the manner similar to that induced by glutamate. These results indicate that delayed neuronal death induced by glutamate is mediated by NO, which is formed by Ca^<2+> influx via NMDA receptors. Glutamate neurotoxicity was significantly ameliorated when the cultures were maintained in the medium containing either methylcobalamin or cyanobalamin. By contrast, acute exposure of cultures to vitamin B_<12> analogs did not affect glutamate neurotoxicity. Glutamate neurotoxicity was reduced by chronic exposure to S-adenosylmethionine, which is formed in the metabolic pathway of methylcobalamin. neurotoxicity induced by sodium nitroprusside was reduced by methylcobalamin and S-adenosylmethionine. These results indicate that chronic exposure to vitamin B_<12> analogs protects cortical neurons against glutamate neurotoxicity by reducing neurotoxic action of NO.
