Transforming growth factor-beta renders ageing microglia inhibitory to oligodendrocyte generation by CNS progenitors.
Fancy, Stephen PJ
Schafer, Dorothy P
John Wiley & Sons Inc.
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Baror, R., Neumann, B., Segel, M., Chalut, K., Fancy, S. P., Schafer, D. P., & Franklin, R. (2019). Transforming growth factor-beta renders ageing microglia inhibitory to oligodendrocyte generation by CNS progenitors.. Glia, 67 (7), 1374-1384. https://doi.org/10.1002/glia.23612
It is now well-established that the macrophages 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 TGFβ. Thus, our findings suggest that the rising levels of circulating TGFβ known to occur with ageing contribute to the age-related decline on remyelination by impairing the ability of microglia to promote oligodendrocyte differentiation from OPCs, and therefore could be a potential therapeutic target to promote remyelination.
Central Nervous System, Microglia, Oligodendroglia, Cells, Cultured, Animals, Animals, Newborn, Rats, Rats, Sprague-Dawley, Transforming Growth Factor beta, Age Factors, Cell Differentiation, Dose-Response Relationship, Drug, Oligodendrocyte Precursor Cells, Cellular Senescence
This work was supported by funding from the UK Multiple Sclerosis Society, Medimmune, The Adelson Medical Research Foundation and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute
Multiple Sclerosis Society (MSS-50)
External DOI: https://doi.org/10.1002/glia.23612
This record's URL: https://www.repository.cam.ac.uk/handle/1810/290043