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Transforming growth factor-beta renders ageing microglia inhibitory to oligodendrocyte generation by CNS progenitors.

Accepted version
Peer-reviewed

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Article

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Authors

Baror, Roey 
Neumann, Björn 
Segel, Michael 
Chalut, Kevin J 
Fancy, Stephen PJ 

Abstract

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.

Description

Keywords

ageing, extracellular matrix, microglia, oligodendrocyte, progenitor cells, Age Factors, Animals, Animals, Newborn, Cell Differentiation, Cells, Cultured, Cellular Senescence, Central Nervous System, Dose-Response Relationship, Drug, Microglia, Oligodendrocyte Precursor Cells, Oligodendroglia, Rats, Rats, Sprague-Dawley, Transforming Growth Factor beta

Journal Title

Glia

Conference Name

Journal ISSN

0894-1491
1098-1136

Volume Title

67

Publisher

Wiley
Sponsorship
Medical Research Council (MC_PC_12009)
Multiple Sclerosis Society (50)
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