title: Oligodendrocytes and progenitors become progressively depleted within chronically demyelinated lesions.
abstract: To understand mechanisms that may underlie the progression of a demyelinated lesion to a chronic state, we have used the cuprizone model of chronic demyelination. In this study, we investigated the fate of oligodendrocytes during the progression of a demyelinating lesion to a chronic state and determined whether transplanted adult oligodendrocyte progenitors could remyelinate the chronically demyelinated axons. Although there is rapid regeneration of the oligodendrocyte population following an acute lesion, most of these newly regenerated cells undergo apoptosis if mice remain on a cuprizone diet. Furthermore, the oligodendrocyte progenitors also become progressively depleted within the lesion, which appears to contribute to the chronic demyelination. Interestingly, even if the mice are returned to a normal diet following 12 weeks of exposure to cuprizone, remyelination and oligodendrocyte regeneration does not occur. However, if adult O4+ progenitors are transplanted into the chronically demyelinated lesion of mice treated with cuprizone for 12 weeks, mature oligodendrocyte regeneration and remyelination occurs after the mice are returned to a normal diet. Thus, the formation of chronically demyelinated lesions induced by cuprizone appears to be the result of oligodendrocyte depletion within the lesion and not due to the inability of the chronically demyelinated axons to be remyelinated.
authors.affiliation: Department of Pathology and the Center for Neurobiology and Behavior, Columbia University, New York, New York, USA. jeffrey.mason@jefferson.edu
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Mason
authors.forename: Arrel
authors.initials: A
authors.lastname: Toews
authors.forename: Janell D
authors.initials: JD
authors.lastname: Hostettler
authors.forename: Pierre
authors.initials: P
authors.lastname: Morell
authors.forename: Kinuko
authors.initials: K
authors.lastname: Suzuki
authors.forename: James E
authors.initials: JE
authors.lastname: Goldman
authors.forename: Glenn K
authors.initials: GK
authors.lastname: Matsushima
mesh_terms: D000818:Animals; D000941:Antigens / Q000737:chemistry; D017209:Apoptosis; D001369:Axons / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation; D003337:Corpus Callosum / Q000473:pathology; D003471:Cuprizone / Q000494:pharmacology; D003711:Demyelinating Diseases / Q000473:pathology*; D018450:Disease Progression; D005982:Glutathione Transferase / Q000378:metabolism; D007150:Immunohistochemistry; D037102:Lectins / Q000737:chemistry; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D009186:Myelin Sheath / Q000737:chemistry; D009836:Oligodendroglia / Q000737:chemistry / Q000378:metabolism*; D020033:Protein Isoforms; D011509:Proteoglycans / Q000737:chemistry; D012313:RNA / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D003471:Cuprizone; D005982:Glutathione Transferase; D037102:Lectins; D020033:Protein Isoforms; D011509:Proteoglycans; D012313:RNA; D011993:Recombinant Fusion Proteins; D000099216:Chondroitin Sulfate Proteoglycan 4