title: Inefficient clearance of myelin debris by microglia impairs remyelinating processes.
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.
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, Neuroscience Laboratory, CHU de Québec Research Center, Laval University, Quebec City, Quebec 2G1V 4G2, Canada.
authors.forename: Antoine
authors.initials: A
authors.lastname: Lampron
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, Neuroscience Laboratory, CHU de Québec Research Center, Laval University, Quebec City, Quebec 2G1V 4G2, Canada.
authors.forename: Antoine
authors.initials: A
authors.lastname: Larochelle
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, Neuroscience Laboratory, CHU de Québec Research Center, Laval University, Quebec City, Quebec 2G1V 4G2, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Laflamme
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, Neuroscience Laboratory, CHU de Québec Research Center, Laval University, Quebec City, Quebec 2G1V 4G2, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Préfontaine
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, Neuroscience Laboratory, CHU de Québec Research Center, Laval University, Quebec City, Quebec 2G1V 4G2, Canada.
authors.forename: Marie-Michèle
authors.initials: MM
authors.lastname: Plante
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, Neuroscience Laboratory, CHU de Québec Research Center, Laval University, Quebec City, Quebec 2G1V 4G2, Canada.
authors.forename: Maria Gabriela
authors.initials: MG
authors.lastname: Sánchez
authors.affiliation: Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors.forename: V Wee
authors.initials: VW
authors.lastname: Yong
authors.affiliation: Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Stys
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, Neuroscience Laboratory, CHU de Québec Research Center, Laval University, Quebec City, Quebec 2G1V 4G2, Canada.
authors.forename: Marie-Ève
authors.initials: MÈ
authors.lastname: Tremblay
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, Neuroscience Laboratory, CHU de Québec Research Center, Laval University, Quebec City, Quebec 2G1V 4G2, Canada serge.rivest@crchudequebec.ulaval.ca.
authors.forename: Serge
authors.initials: S
authors.lastname: Rivest
mesh_terms: D000818:Animals; D001369:Axons / Q000276:immunology* / Q000473:pathology; D001854:Bone Marrow Cells / Q000276:immunology* / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1; D003711:Demyelinating Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology* / Q000473:pathology; D009186:Myelin Sheath / Q000276:immunology* / Q000473:pathology; D010586:Phagocytes / Q000276:immunology* / Q000473:pathology; D054390:Receptors, CCR2 / Q000235:genetics / Q000276:immunology; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515335:Ccr2 protein, mouse; C471885:Cx3cr1 protein, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine