title: Cortical demyelination is prominent in the murine cuprizone model and is strain-dependent.
abstract: The cuprizone model of toxic demyelination in the central nervous system is commonly used to investigate the pathobiology of remyelination in the corpus callosum. However, in human demyelinating diseases such as multiple sclerosis, recent evidence indicates a considerable amount of cortical demyelination in addition to white matter damage. Therefore, we have investigated cortical demyelination in the murine cuprizone model. To induce demyelination, C57BL/6 mice were challenged with 0.2% cuprizone feeding for 6 weeks followed by a recovery phase of 6 weeks with a cuprizone-free diet. In addition to the expected demyelination in the corpus callosum, the cortex of C57BL/6 mice was completely demyelinated after 6 weeks of cuprizone feeding. After withdrawal of cuprizone the cortex showed complete remyelination similar to that in the corpus callosum. When C57BL/6 mice were fed cuprizone for a prolonged period of 12 weeks, cortical remyelination was significantly delayed. Because interstrain differences have been described, we also investigated the effects of cuprizone on cortical demyelination in BALB/cJ mice. In these mice, cortical demyelination was only partial. Moreover, cortical microglia accumulation was markedly increased in BALB/cJ mice, whereas microglia were absent in the cortex of C57BL/6 mice. In summary, our results show that cuprizone feeding is an excellent model in which to study cortical demyelination and remyelination, including contributing genetic factors represented by strain differences.
authors: Department of Neurology, Medical School of Hannover, Carl-Neuberg-Strasse-1, Hanover, Germany.
authors: Thomas
authors: T
authors: Skripuletz
authors: Maren
authors: M
authors: Lindner
authors: Alexandra
authors: A
authors: Kotsiari
authors: Niklas
authors: N
authors: Garde
authors: Jantje
authors: J
authors: Fokuhl
authors: Franziska
authors: F
authors: Linsmeier
authors: Corinna
authors: C
authors: Trebst
authors: Martin
authors: M
authors: Stangel
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology*; D003337:Corpus Callosum / Q000187:drug effects / Q000473:pathology; D003471:Cuprizone / Q000633:toxicity*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009186:Myelin Sheath / Q000187:drug effects* / Q000473:pathology*; D013997:Time Factors
chemical_list: D005904:Glial Fibrillary Acidic Protein; D003471:Cuprizone