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Extracellular signal-regulated kinase 1/2 signaling promotes oligodendrocyte myelination in vitro.
- Source :
-
Journal of neurochemistry [J Neurochem] 2012 Sep; Vol. 122 (6), pp. 1167-80. Date of Electronic Publication: 2012 Aug 03. - Publication Year :
- 2012
-
Abstract
- Multiple extracellular factors have been implicated in orchestrating myelination of the CNS; however, less is known about the intracellular signaling cascades that regulate this process. We have previously shown that brain-derived neurotrophic factor (BDNF) promotes oligodendrocyte myelination. Here, we screened for the activation of candidate signaling pathways in in vitro myelination assays and found that extracellular signal-regulated kinase (Erk) signaling positively correlated with basal levels of oligodendrocyte myelination as well as BDNF-induced myelination in vitro. By selectively manipulating Erk1/2 activation in oligodendrocytes in vitro, we found that constitutive activation of Erk1/2 significantly increased myelination, mimicking the promyelinating effect of BDNF, and also caused myelination to occur earlier. Conversely, selective inhibition of Erk1/2 in oligodendrocytes significantly reduced the basal level of myelination and blocked the promyelinating effect of BDNF. Analysis of myelinating spinal cord and corpus callosum white matter tracts revealed that the majority of mature oligodendrocytes are co-labeled with phospho-Erk1/2, whereas phospho-Erk1/2 was rarely observed in oligodendrocyte progenitor cells. Finally, the total level of phospho-Erk1/2 correlated with myelin formation during the early postnatal period. Collectively, these data identify that Erk1/2 signaling within oligodendrocytes exerts an important and direct effect to promote myelination.<br /> (© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.)
- Subjects :
- Animals
Brain-Derived Neurotrophic Factor metabolism
Brain-Derived Neurotrophic Factor physiology
Cell Communication physiology
Cells, Cultured
Coculture Techniques
Female
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 3 physiology
Oligodendroglia physiology
Rats
Rats, Sprague-Dawley
MAP Kinase Signaling System physiology
Myelin Sheath physiology
Oligodendroglia cytology
Oligodendroglia enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1471-4159
- Volume :
- 122
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 22784206
- Full Text :
- https://doi.org/10.1111/j.1471-4159.2012.07871.x