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Extracellular Acidic pH Inhibits Oligodendrocyte Precursor Viability, Migration, and Differentiation

Author(s)
Jagielska, Anna; Wilhite, Kristen D.; Van Vliet, Krystyn J.
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Abstract
Axon remyelination in the central nervous system requires oligodendrocytes that produce myelin. Failure of this repair process is characteristic of neurodegeneration in demyelinating diseases such as multiple sclerosis, and it remains unclear how the lesion microenvironment contributes to decreased remyelination potential of oligodendrocytes. Here, we show that acidic extracellular pH, which is characteristic of demyelinating lesions, decreases the migration, proliferation, and survival of oligodendrocyte precursor cells (OPCs), and reduces their differentiation into oligodendrocytes. Further, OPCs exhibit directional migration along pH gradients toward acidic pH. These in vitro findings support a possible in vivo scenario whereby pH gradients attract OPCs toward acidic lesions, but resulting reduction in OPC survival and motility in acid decreases progress toward demyelinated axons and is further compounded by decreased differentiation into myelin-producing oligodendrocytes. As these processes are integral to OPC response to nerve demyelination, our results suggest that lesion acidity could contribute to decreased remyelination.
Date issued
2013-09
URI
http://hdl.handle.net/1721.1/83527
Department
Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Materials Science and Engineering
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Jagielska, Anna, Kristen D. Wilhite, and Krystyn J. Van Vliet. “Extracellular Acidic pH Inhibits Oligodendrocyte Precursor Viability, Migration, and Differentiation.” Edited by Martin Stangel. PLoS ONE 8, no. 9 (September 30, 2013): e76048.
Version: Final published version
ISSN
1932-6203

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