title: Cuprizone induces similar demyelination in male and female C57BL/6 mice and results in disruption of the estrous cycle.
abstract: Multiple sclerosis is a demyelinating neurological disease that is influenced by gender, primarily reflected in greater susceptibility to disease development in women than in men. Cuprizone intoxication, an animal model that is used to study demyelination and remyelination, has been extensively characterized in male C57BL/6 mice. Here, we have undertaken a comprehensive characterization of the morphological and cellular processes that occur in female C57BL/6J mice during cuprizone-induced demyelination and subsequent remyelination and compared them with age-matched male mice. We find that the pattern of demyelination and remyelination is similar between genders and that there is little or no difference in the loss or repopulation of mature oligodendrocytes or accumulation of reactive glia. Furthermore, examination of alphaERKO and betaERKO mice suggests that estrogen receptors do not affect the outcome for demyelination or remyelination. Interestingly, we found that cuprizone treatment disrupts estrous cyclicity in female mice, possibly interfering with potential hormone influences on demyelination and remyelination. Therefore, cuprizone-induced demyelination in C57BL/6J mice may have limitations as a model for the study of sex differences.
authors.affiliation: Curriculum in Neurobiology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Lorelei C
authors.initials: LC
authors.lastname: Taylor
authors.forename: Wendy
authors.initials: W
authors.lastname: Gilmore
authors.forename: Jenny P-Y
authors.initials: JP
authors.lastname: Ting
authors.forename: Glenn K
authors.initials: GK
authors.lastname: Matsushima
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002614:Chelating Agents / Q000633:toxicity*; D003337:Corpus Callosum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D030762:Estrous Cycle / Q000187:drug effects*; D005260:Female; D005835:Genitalia / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D012727:Sex Characteristics
chemical_list: D002614:Chelating Agents; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D003471:Cuprizone