Identification of a microglia phenotype supportive of remyelination

M Olah, S Amor, N Brouwer, J Vinet, B Eggen, K Biber… - Glia, 2012 - Wiley Online Library
M Olah, S Amor, N Brouwer, J Vinet, B Eggen, K Biber, HWGM Boddeke
Glia, 2012Wiley Online Library
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 …
Abstract
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.
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