Inefficient clearance of myelin debris by microglia impairs remyelinating processes.

TitleInefficient clearance of myelin debris by microglia impairs remyelinating processes.
Publication TypeJournal Article
Year of Publication2015
AuteursLampron, A, Larochelle, A, Laflamme, N, Préfontaine, P, Plante, M-M, Sánchez, MGabriela, V Yong, W, Stys, PK, Tremblay, M-È, Rivest, S
JournalJ Exp Med
Volume212
Issue4
Pagination481-95
Date Published2015 Apr 06
ISSN1540-9538
KeywordsAnimals, Axons, Bone Marrow Cells, CX3C Chemokine Receptor 1, Demyelinating Diseases, Mice, Mice, Knockout, Microglia, Myelin Sheath, Phagocytes, Receptors, CCR2, Receptors, Chemokine
Abstract

An imbalance between remyelinating and demyelinating rates underlies degenerative processes in demyelinating diseases such as multiple sclerosis. An optimal therapeutic strategy would be to stimulate remyelination while limiting demyelination. Although accumulation of myelin debris impairs remyelination, the mechanisms regulating the clearance of such debris by mononuclear phagocytic cells are poorly understood. We demonstrate that after cuprizone intoxication, CCR2-dependent infiltration of mouse bone marrow-derived cells is abundant in demyelinating areas, but that these cells do not impact demyelination. However, in CX3CR1-deficient mice, the clearance of myelin debris by microglia was blocked greatly, affecting the integrity of the axon and myelin sheaths and thus preventing proper remyelination. These results highlight the crucial role played by CX3CR1 in myelin removal and show that there can be no efficient remyelination after a primary demyelinating insult if myelin clearance by microglia is impaired.

DOI10.1084/jem.20141656
Alternate JournalJ. Exp. Med.
PubMed ID25779633
PubMed Central IDPMC4387282
Grant List / / Canadian Institutes of Health Research / Canada