Protective effects of methylcobalamin, a vitamin B12 analog, against glutamate-induced neurotoxicity in retinal cell culture.
OBJECTIVE
To examine the effects of methylcobalamin on glutamate-induced neurotoxicity in the cultured retinal neurons.


METHODS
Primary cultures obtained from the fetal rat retina (gestation days 16 to 19) were used for the experiment. The neurotoxicity was assessed quantitatively using the trypan blue exclusion method.


RESULTS
Glutamate neurotoxicity was prevented by chronic exposure to methylcobalamin and S-adenosylmethionine (SAM), which is formed in the metabolic pathway of methylcobalamin. Chronic exposure to methylcobalamin and SAM also inhibited the neurotoxicity induced by sodium nitroprusside that release nitric oxide. By contrast, acute exposure to methylcobalamin did not protect retinal neurons against glutamate neurotoxicity.


CONCLUSIONS
Chronic administration of methylcobalamin protects cultured retinal neurons against N-methyl-D-aspartate-receptor-mediated glutamate neurotoxicity, probably by altering the membrane properties through SAM-mediated methylation.
Kikuchi
M
M
Department of Ophthalmology, Graduate School of Medicine, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Kashii
S
S
Honda
Y
Y
Tamura
Y
Y
Kaneda
K
K
Akaike
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004396:Coloring Agents; D018698:Glutamic Acid / Q000633:toxicity*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D009599:Nitroprusside / Q000633:toxicity; D051381:Rats; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D012436:S-Adenosylmethionine / Q000494:pharmacology; D013439:Sulfhydryl Reagents / Q000633:toxicity; D014343:Trypan Blue; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000494:pharmacology
D004396:Coloring Agents; D013439:Sulfhydryl Reagents; D009599:Nitroprusside; D018698:Glutamic Acid; D012436:S-Adenosylmethionine; C019476:mecobalamin; D014343:Trypan Blue; D014805:Vitamin B 12; D002118:Calcium