mCSF-Induced Microglial Activation Prevents Myelin Loss and Promotes Its Repair in a Mouse Model of Multiple Sclerosis.

TitlemCSF-Induced Microglial Activation Prevents Myelin Loss and Promotes Its Repair in a Mouse Model of Multiple Sclerosis.
Publication TypeJournal Article
Year of Publication2018
AuthorsLaflamme, N, Cisbani, G, Préfontaine, P, Srour, Y, Bernier, J, St-Pierre, M-K, Tremblay, M-È, Rivest, S
JournalFront Cell Neurosci
Volume12
Pagination178
Date Published2018
ISSN1662-5102
Abstract

A pathological hallmark of multiple sclerosis (MS) is myelin loss in brain white matter accompanied by compromised remyelination. Demyelinated lesions are deeply associated with oligodendrocyte apoptosis and a robust inflammatory response. Although various studies point towards a noxious role of inflammation in MS, others emphasize a positive role for the innate immune cells in disease progression. A cytokine well-known to stimulate cell survival, proliferation and differentiation of myeloid cells, macrophage colony-stimulating factor (mCSF), was administered to mice during a 5 week-long cuprizone diet. Treated mice exhibited reduced myelin loss during the demyelination phase, together with an increased number of microglia and oligodendrocyte precursor cells in lesion sites. Tamoxifen-induced conditional deletion of the mCSF receptor in microglia from cuprizone-fed mice caused aberrant myelin debris accumulation in the corpus callosum and reduced microglial phagocytic response. mCSF therefore plays a key role in stimulating myelin clearance by the brain innate immune cells, which is a prerequisite for proper remyelination and myelin repair processes.

DOI10.3389/fncel.2018.00178
Alternate JournalFront Cell Neurosci
PubMed ID30018535
PubMed Central IDPMC6037698