title: Age increases axon loss associated with primary demyelination in cuprizone-induced demyelination in C57BL/6 mice.
abstract: Axon loss is recognised as a significant contributor to the progression of the disability associated with multiple sclerosis. Although evidence of axon damage is found in areas of chronic demyelination it is more frequently seen in association with acute demyelination. This study compares the incidence of axon degeneration associated with the areas undergoing demyelination in young adult (8-10 weeks) and aged (6-7 months) C57BL/6 mice in cuprizone intoxication; a widely used model of demyelination. The incidence of axon transection, as indicated by the presence of SMI 32 positive axonal spheroids, and evidence of axon loss in the medial corpus callosum, were significantly greater in aged mice, as was the magnitude of the macrophage and astrocyte response to demyelination. Aged C57BL/6 mice are thus more prone to axon degeneration in association with demyelination than young adult mice. A retrospective study indicated that the incidence of axon degeneration was much higher in C57BL/6 mice than in the Swiss albino mice used in the early cuprizone intoxication studies which were fed much higher doses of cuprizone. These results indicate both a genetic and age susceptibility to demyelination-associated axon transection.
authors.affiliation: Department of Veterinary Medicine, MS Society Cambridge Centre for Myelin Repair, Madingley Road, Cambridge CB3 OES, UK.
authors.forename: K-A
authors.initials: KA
authors.lastname: Irvine
authors.forename: W F
authors.initials: WF
authors.lastname: Blakemore
mesh_terms: D000375:Aging / Q000187:drug effects / Q000276:immunology*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000276:immunology* / Q000473:pathology* / Q000648:ultrastructure; D003337:Corpus Callosum / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D003471:Cuprizone