title: Microglial recruitment, activation, and proliferation in response to primary demyelination.
abstract: We have characterized the cellular response to demyelination/remyelination in the central nervous system using the toxin cuprizone, which causes reproducible demyelination in the corpus callosum. Microglia were distinguished from macrophages by relative CD45 expression (CD45(dim)) using flow cytometry. Their expansion occurred rapidly and substantially outnumbered infiltrating macrophages and T cells throughout the course of cuprizone treatment. We used bromodeoxyuridine incorporation and bone marrow chimeras to show that both proliferation and immigration from blood accounted for increased microglial numbers. Microglia adopted an activated phenotype during demyelination, up-regulating major histocompatibility class I and B7.2/CD86. A subpopulation of CD45(dim-high) microglia that expressed reduced levels of CD11b emerged during demyelination. These microglia expressed CD11c and were potent antigen-presenting cells in vitro. T cells were recruited to the demyelinated corpus callosum but did not appear to be activated. Our study highlights the role of microglia as a heterogeneous population of cells in primary demyelination, with the capacity to present antigen, proliferate, and migrate into demyelinated areas.
authors: Montreal Neurological Institute, McGill University, Montreal, Canada.
authors: Leah T
authors: LT
authors: Remington
authors: Alicia A
authors: AA
authors: Babcock
authors: Simone P
authors: SP
authors: Zehntner
authors: Trevor
authors: T
authors: Owens
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003337:Corpus Callosum / Q000276:immunology* / Q000473:pathology*; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D008996:Monoamine Oxidase Inhibitors; D003471:Cuprizone