Females remyelinate more efficiently than males following demyelination in the aged but not young adult CNS

Abstract

To assess the effects of sex on CNS remyelination, demyelinating lesions were induced by injection of ethidium bromide into the caudal cerebellar peduncle of Sprague-Dawley rats divided into the following 8 groups: young adult male, young adult female, old adult male and old adult female and each of these in which the gonads had been removed 4 weeks prior to lesion induction. Remyelination was assessed, blinded to grouping, by a ranking analysis using standard morphological criteria. In young adult animals, where remyelination proceeds rapidly, there was no difference in the remyelination at four weeks after lesion induction in male or females regardless of whether they were intact or castrated/ovariectomised. However, in old adult rats, where remyelination proceeds slowly, the extent of oligodendrocyte remyelination was significantly less in males compared to females at 8 weeks after lesion induction. Removal of gonads did not affect remyelination in old rats of either gender. These results indicate a sex-associated divergence in remyelination efficiency that occurs with ageing that is unaffected by the removal of gonadal sources of sex steroid hormones.