Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle and promotes nerve regeneration in a rat sciatic nerve injury model

Kiyoshi Okada; Hiroyuki Tanaka; Ko Temporin; Michio Okamoto; Yusuke Kuroda; Hisao Moritomo; Tsuyoshi Murase; Hideki Yoshikawa

doi:10.1016/j.expneurol.2009.12.017

Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle and promotes nerve regeneration in a rat sciatic nerve injury model

Exp Neurol. 2010 Apr;222(2):191-203. doi: 10.1016/j.expneurol.2009.12.017. Epub 2010 Jan 4.

Authors

Kiyoshi Okada¹, Hiroyuki Tanaka, Ko Temporin, Michio Okamoto, Yusuke Kuroda, Hisao Moritomo, Tsuyoshi Murase, Hideki Yoshikawa

Affiliation

¹ Department of Orthopaedics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.

PMID: 20045411
DOI: 10.1016/j.expneurol.2009.12.017

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Action Potentials / drug effects
Animals
Brain-Derived Neurotrophic Factor / pharmacology
Cell Proliferation / drug effects
Cell Survival / drug effects
Cells, Cultured
Disease Models, Animal
Dose-Response Relationship, Drug
Electromyography
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology
Extracellular Signal-Regulated MAP Kinases / metabolism*
Female
Ganglia, Spinal / cytology
In Situ Nick-End Labeling / methods
Methylation / drug effects
Motor Activity / drug effects
Muscle, Skeletal / physiopathology
Nerve Regeneration / drug effects*
Neurites / drug effects
Neurons / cytology
Neurons / drug effects
Neurons / metabolism
Oncogene Protein v-akt / metabolism*
Rats
Rats, Wistar
Recovery of Function / drug effects
Sciatic Neuropathy / blood
Sciatic Neuropathy / drug therapy*
Sciatic Neuropathy / physiopathology
Sensation / drug effects
Tubulin / metabolism
Vitamin B 12 / analogs & derivatives*
Vitamin B 12 / blood
Vitamin B 12 / therapeutic use

Substances

Brain-Derived Neurotrophic Factor
Enzyme Inhibitors
Tubulin
mecobalamin
Oncogene Protein v-akt
Extracellular Signal-Regulated MAP Kinases
Vitamin B 12