Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle and promotes nerve regeneration in a rat sciatic nerve injury model.
Methylcobalamin is a vitamin B12 analog and is necessary for the maintenance of the nervous system. Although some previous studies have referred to the effects of methylcobalamin on neurons, the precise mechanism of this effect remains obscure. Here we show that methylcobalamin at concentrations above 100 nM promotes neurite outgrowth and neuronal survival and that these effects are mediated by the methylation cycle, a metabolic pathway involving methylation reactions. We also demonstrate that methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle. In a rat sciatic nerve injury model, continuous administration of high doses of methylcobalamin improves nerve regeneration and functional recovery. Therefore, methylcobalamin may provide the basis for better treatments of nervous disorders through effective systemic or local delivery of high doses of methylcobalamin to target organs.
Okada
Kiyoshi
K
Department of Orthopaedics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Tanaka
Hiroyuki
H
Temporin
Ko
K
Okamoto
Michio
M
Kuroda
Yusuke
Y
Moritomo
Hisao
H
Murase
Tsuyoshi
T
Yoshikawa
Hideki
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D020287:In Situ Nick-End Labeling / Q000379:methods; D008745:Methylation / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018482:Muscle, Skeletal / Q000503:physiopathology; D009416:Nerve Regeneration / Q000187:drug effects*; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects; D020426:Sciatic Neuropathy / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D012677:Sensation / Q000187:drug effects; D014404:Tubulin / Q000378:metabolism; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D014404:Tubulin; C019476:mecobalamin; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D014805:Vitamin B 12