p38 MAP kinase regulation of oligodendrocyte differentiation with CREB as a potential target

Neurochem Res. 2007 Feb;32(2):293-302. doi: 10.1007/s11064-006-9274-9. Epub 2007 Jan 19.


Despite a substantial understanding of the factors regulating oligodendrocyte differentiation, the signaling mechanisms involved in this process are not well-understood. This study elaborates on the findings (Bhat NR, Zhang P (1997) FASEB J 11:A925; Baron W, Metz B, Bansal R, Hoekstra D, de Vries H (2000) Mol Cell Neurosci 15:314-329) of a role for p38 MAP kinase signaling in oligodendrocyte differentiation and myelin gene expression. When proliferating oligodendrocyte progenitors were switched to a growth factor-free differentiation medium, there was a rapid activation of p38 kinase that correlated with an increased phosphorylation of CREB, a down-stream target and a factor involved in oligodendrocyte differentiation. Addition of forskolin, a known inducer of intracellular c-AMP and of oligodendrocyte differentiation, also stimulated CREB phosphorylation in a p38 kinase dependent way. Pharmacological inhibition of p38 interfered with the morphological and antigenic changes associated with differentiating oligodendrocytes as well as with the developmental and forskolin-induced expression of myelin basic protein, thereby supporting an essential role for p38 MAPK pathway in oligodendrocyte differentiation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Colforsin / pharmacology
  • Cyclic AMP Response Element-Binding Protein / physiology*
  • Enzyme Activation
  • Imidazoles / pharmacology
  • Myelin Basic Protein / biosynthesis
  • Myelin Proteolipid Protein / biosynthesis
  • Myelin-Associated Glycoprotein / biosynthesis
  • Oligodendroglia / cytology*
  • Oligodendroglia / drug effects
  • Phosphorylation / drug effects
  • Pyridines / pharmacology
  • RNA, Messenger / antagonists & inhibitors
  • Rats
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / physiology*


  • Cyclic AMP Response Element-Binding Protein
  • Imidazoles
  • Myelin Basic Protein
  • Myelin Proteolipid Protein
  • Myelin-Associated Glycoprotein
  • Pyridines
  • RNA, Messenger
  • Colforsin
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580