Protective effects of a vitamin B12 analog, methylcobalamin, against glutamate cytotoxicity in cultured cortical neurons.
The effects of methylcobalamin, a vitamin B12 analog, on glutamate-induced neurotoxicity were examined using cultured rat cortical neurons. Cell viability was markedly reduced by a brief exposure to glutamate followed by incubation with glutamate-free medium for 1 h. Glutamate cytotoxicity was prevented when the cultures were maintained in methylcobalamin-containing medium. Glutamate cytotoxicity was also prevented by chronic exposure to S-adenosylmethionine, which is formed in the metabolic pathway of methylcobalamin. Chronic exposure to methylcobalamin and S-adenosylmethionine also inhibited the cytotoxicity induced by N-methyl-D-aspartate or sodium nitroprusside that releases nitric oxide. In cultures maintained in a standard medium, glutamate cytotoxicity was not affected by adding methylcobalamin to the glutamate-containing medium. In contrast, acute exposure to MK-801, a NMDA receptor antagonist, prevented glutamate cytotoxicity. These results indicate that chronic exposure to methylcobalamin protects cortical neurons against NMDA receptor-mediated glutamate cytotoxicity.
Akaike
A
A
Department of Neuropharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Japan.
Tamura
Y
Y
Sato
Y
Y
Yokota
T
T
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D005971:Glutamates / Q000633:toxicity; D018698:Glutamic Acid; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000633:toxicity; D009474:Neurons / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009599:Nitroprusside / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D012436:S-Adenosylmethionine / Q000494:pharmacology; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D018377:Neurotransmitter Agents; D009599:Nitroprusside; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D012436:S-Adenosylmethionine; C019476:mecobalamin; D014805:Vitamin B 12