Mammalian target of rapamycin (mTOR) is involved in the neuronal differentiation of neural progenitors induced by insulin

Mol Cell Neurosci. 2008 Sep;39(1):118-24. doi: 10.1016/j.mcn.2008.06.003. Epub 2008 Jun 17.

Abstract

The fate of neural progenitor cells (NPCs) is determined by many extracellular cues. Among them, insulin and insulin-like growth factor (IGF) family are found to promote the neuronal differentiation of NPCs. Akt activation has been indicated to be responsible for the insulin/IGF-I induced neuronal differentiation. However, the mechanism by which insulin/IGF-I-PI3K-Akt pathway induces neurogenesis of NPCs is not clear. In this study, we have demonstrated that mTOR is involved in the insulin-induced neuronal differentiation. Insulin induces neurogenesis of NPCs in a dose-dependent manner. Phosphorylated mTOR has been up-regulated in a PI3K-Akt dependent manner during NPC differentiation induced by insulin. The specific inhibitor of mTOR, rapamycin, can abrogate the increase of differentiated neurons stimulated by insulin. In addition, this is not the result from the apoptosis of neurons or NPCs. This research has extended the understanding of functions of mTOR and the mechanism of NPC differentiation regulated by insulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Differentiation / drug effects*
  • Cell Differentiation / physiology
  • Dose-Response Relationship, Drug
  • Humans
  • Immunosuppressive Agents / metabolism
  • Insulin / pharmacology*
  • Neurons / cytology
  • Neurons / physiology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / physiology
  • Sirolimus / metabolism
  • Stem Cells* / drug effects
  • Stem Cells* / physiology
  • TOR Serine-Threonine Kinases

Substances

  • Immunosuppressive Agents
  • Insulin
  • Protein Kinases
  • Phosphatidylinositol 3-Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Sirolimus