PMID- 22784206 OWN - NLM STAT- MEDLINE DCOM- 20121121 LR - 20220309 IS - 1471-4159 (Electronic) IS - 0022-3042 (Linking) VI - 122 IP - 6 DP - 2012 Sep TI - Extracellular signal-regulated kinase 1/2 signaling promotes oligodendrocyte myelination in vitro. PG - 1167-80 LID - 10.1111/j.1471-4159.2012.07871.x [doi] AB - 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. CI - (c) 2012 The Authors. Journal of Neurochemistry (c) 2012 International Society for Neurochemistry. FAU - Xiao, Junhua AU - Xiao J AD - Centre for Neuroscience Research, The University of Melbourne, Victoria, Australia. xiaoj@unimelb.edu.au FAU - Ferner, Anita H AU - Ferner AH FAU - Wong, Agnes W AU - Wong AW FAU - Denham, Mark AU - Denham M FAU - Kilpatrick, Trevor J AU - Kilpatrick TJ FAU - Murray, Simon S AU - Murray SS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120803 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Brain-Derived Neurotrophic Factor) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism/physiology MH - Cell Communication/physiology MH - Cells, Cultured MH - Coculture Techniques MH - Female MH - MAP Kinase Signaling System/*physiology MH - Mice MH - Mice, Inbred C57BL MH - Mitogen-Activated Protein Kinase 3/physiology MH - Myelin Sheath/*physiology MH - Oligodendroglia/*cytology/*enzymology/physiology MH - Rats MH - Rats, Sprague-Dawley EDAT- 2012/07/13 06:00 MHDA- 2012/12/10 06:00 CRDT- 2012/07/13 06:00 PHST- 2012/07/13 06:00 [entrez] PHST- 2012/07/13 06:00 [pubmed] PHST- 2012/12/10 06:00 [medline] AID - 10.1111/j.1471-4159.2012.07871.x [doi] PST - ppublish SO - J Neurochem. 2012 Sep;122(6):1167-80. doi: 10.1111/j.1471-4159.2012.07871.x. Epub 2012 Aug 3.