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p38 MAP Kinase Regulation of Oligodendrocyte Differentiation with CREB as a Potential Target

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Abstract

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.

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Acknowledgments

This study was supported by NIH grant R01NS41396.

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Correspondence to Narayan R. Bhat.

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Special issue dedicated to Anthony Campagnoni.

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Bhat, N.R., Zhang, P. & Mohanty, S.B. p38 MAP Kinase Regulation of Oligodendrocyte Differentiation with CREB as a Potential Target. Neurochem Res 32, 293–302 (2007). https://doi.org/10.1007/s11064-006-9274-9

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  • DOI: https://doi.org/10.1007/s11064-006-9274-9

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