Identification of a microglia phenotype supportive of remyelination
Version of Record online: 9 NOV 2011
Copyright © 2011 Wiley Periodicals, Inc.
Volume 60, Issue 2, pages 306–321, February 2012
How to Cite
Olah, M., Amor, S., Brouwer, N., Vinet, J., Eggen, B., Biber, K. and Boddeke, H. W. G. M. (2012), Identification of a microglia phenotype supportive of remyelination. Glia, 60: 306–321. doi: 10.1002/glia.21266
- Issue online: 5 DEC 2011
- Version of Record online: 9 NOV 2011
- Manuscript Accepted: 11 OCT 2011
- Manuscript Received: 14 JUL 2011
- Alzheimer Society of Canada/CIHR/Astra Zeneca Canada
- microglia phenotype;
- preactive lesions
In multiple sclerosis, endogenous oligodendrocyte precursor cells (OPCs) attempt to remyelinate areas of myelin damage. During disease progression, however, these attempts fail. It has been suggested that modulating the inflammatory environment of the lesion might provide a promising therapeutic approach to promote endogenous remyelination. Microglia are known to play a central role in neuroinflammatory processes. To investigate the microglia phenotype that supports remyelination, we performed genome-wide gene expression analysis of microglia from the corpus callosum during demyelination and remyelination in the mouse cuprizone model, in which remyelination spontaneously occurs after an episode of toxin-induced primary demyelination. We provide evidence for the existence of a microglia phenotype that supports remyelination already at the onset of demyelination and persists throughout the remyelination process. Our data show that microglia are involved in the phagocytosis of myelin debris and apoptotic cells during demyelination. Furthermore, they express a cytokine and chemokine repertoire enabling them to activate and recruit endogenous OPCs to the lesion site and deliver trophic support during remyelination. This study not only provides a detailed transcriptomic analysis of the remyelination-supportive microglia phenotype but also reinforces the notion that the primary function of microglia is the maintenance of tissue homeostasis and the support of regeneration already at the earliest stages in the development of demyelinating lesions. © 2011 Wiley Periodicals, Inc.