Akt/mammalian target of rapamycin signaling pathway regulates neurite outgrowth in cerebellar granule neurons stimulated by methylcobalamin

Neurosci Lett. 2011 May 20;495(3):201-4. doi: 10.1016/j.neulet.2011.03.065. Epub 2011 Mar 30.

Abstract

Methylcobalamin (MeCbl), a vitamin B12 analog, promotes neurite outgrowth by activating Akt in neurons. However, Akt is involved in many cellular functions, and the downstream signal of Akt that promotes neurite outgrowth in neurons in the presence of MeCbl remains obscure. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that regulates multiple cellular functions including neurite outgrowth. mTOR is regarded as important for the regeneration of injured nerves. In this study, we examined the relationship between MeCbl and mTOR activity and found that MeCbl increases mTOR activity via the activation of Akt and promotes neurite outgrowth in cerebellar granule neurons via the activation of mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Cerebellum / cytology*
  • Chromones / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • Morpholines / pharmacology
  • Neurites / drug effects*
  • Neurons / cytology*
  • Neurons / drug effects
  • Oncogene Protein v-akt / metabolism*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / metabolism*
  • Vitamin B 12 / analogs & derivatives*
  • Vitamin B 12 / pharmacology

Substances

  • Chromones
  • Enzyme Inhibitors
  • Morpholines
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • mecobalamin
  • mTOR protein, rat
  • Oncogene Protein v-akt
  • TOR Serine-Threonine Kinases
  • Vitamin B 12
  • Sirolimus