title: Identification of a microglia phenotype supportive of remyelination.
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.
authors.affiliation: Department of Neuroscience, Section Medical Physiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Marta
authors.initials: M
authors.lastname: Olah
authors.forename: Sandra
authors.initials: S
authors.lastname: Amor
authors.forename: Nieske
authors.initials: N
authors.lastname: Brouwer
authors.forename: Jonathan
authors.initials: J
authors.lastname: Vinet
authors.forename: Bart
authors.initials: B
authors.lastname: Eggen
authors.forename: Knut
authors.initials: K
authors.lastname: Biber
authors.forename: Hendrikus W G M
authors.initials: HW
authors.lastname: Boddeke
mesh_terms: D000818:Animals; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D010641:Phenotype