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Transforming growth factor‐beta renders ageing microglia inhibitory to oligodendrocyte generation by CNS progenitors
Author(s) -
Baror Roey,
Neumann Björn,
Segel Michael,
Chalut Kevin J.,
Fancy Stephen P. J.,
Schafer Dorothy P.,
Franklin Robin J. M.
Publication year - 2019
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23612
Subject(s) - remyelination , microglia , biology , oligodendrocyte , myelin , neuroscience , progenitor cell , ageing , central nervous system , microbiology and biotechnology , immunology , stem cell , inflammation , genetics
It 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 TGFβ. Thus, our findings suggest that the rising levels of circulating TGFβ 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.