UMMS Affiliation

Department of Neurobiology; Brudnik Neuropsychiatric Institute; Schafer Lab

Publication Date

2019-03-12

Document Type

Article

Disciplines

Cellular and Molecular Physiology | Nervous System | Neuroscience and Neurobiology

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 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.

Keywords

ageing, extracellular matrix, microglia, oligodendrocyte, progenitor cells

Rights and Permissions

© 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.

DOI of Published Version

10.1002/glia.23612

Source

Glia. 2019 Mar 12. doi: 10.1002/glia.23612. [Epub ahead of print] Link to article on publisher's site

Journal/Book/Conference Title

Glia

Related Resources

Link to Article in PubMed

PubMed ID

30861188

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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