Transforming growth factor-beta renders ageing microglia inhibitory to oligodendrocyte generation by CNS progenitors
Chalut, Kevin J.
Fancy, Stephen P.J. J
Schafer, Dorothy P
Franklin, Robin J.M.
UMass Chan AffiliationsSchafer Lab
Brudnick Neuropsychiatric Research Institute
Document TypeJournal Article
Cellular and Molecular Physiology
Neuroscience and Neurobiology
MetadataShow full item record
AbstractIt is now well-established that the macrophage and microglial response to CNS demyelination influences remyelination by removing myelin debris and secreting a variety of signaling molecules that influence the behaviour of oligodendrocyte progenitor cells (OPCs). Previous studies have shown that changes in microglia contribute to the age-related decline in the efficiency of remyelination. In this study, we show that microglia increase their expression of the proteoglycan NG2 with age, and that this is associated with an altered micro-niche generated by aged, but not young, microglia that can divert the differentiation OPCs from oligodendrocytes into astrocytes in vitro. We further show that these changes in ageing microglia are generated by exposure to high levels of TGFbeta. Thus, our findings suggest that the rising levels of circulating TGFbeta known to occur with ageing contribute to the age-related decline in remyelination by impairing the ability of microglia to promote oligodendrocyte differentiation from OPCs, and therefore could be a potential therapeutic target to promote remyelination.
Glia. 2019 Mar 12. doi: 10.1002/glia.23612. [Epub ahead of print] Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/37964
Rights© 2019 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as © 2019 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.