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Extracellular signal‐regulated kinase 1/2 signaling promotes oligodendrocyte myelination in vitro
Author(s) -
Xiao Junhua,
Ferner Anita H,
Wong Agnes W,
Denham Mark,
Kilpatrick Trevor J,
Murray Simon S
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07871.x
Subject(s) - oligodendrocyte , biology , extracellular , mapk/erk pathway , microbiology and biotechnology , neuroscience , signal transduction , neurotrophic factors , myelin , brain derived neurotrophic factor , corpus callosum , central nervous system , biochemistry , receptor
J. Neurochem. (2012) 122 , 1167–1180. 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.