Sex differences and the protective influence of estrogen in a mouse model of demyelinating disease

Sex differences and the protective influence of estrogen in a mouse model of demyelinating disease Public Deposited

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Taylor, Lorelei Carissa
- Affiliation: School of Medicine, UNC Neuroscience Center, Neuroscience Curriculum

Abstract

Demyelinating diseases such as multiple sclerosis may be influenced by gender dimorphisms and sex hormones. Here, the cuprizone model of toxin-induced oligodendrocyte death and demyelination was used to investigate sex differences in two mouse strains, SJL and C57BL/6. The results indicate that female SJL mice are partially protected from oligodendrocyte loss and demyelination compared to their male counterparts. No sex differences were exhibited in the C57BL/6 strain. Furthermore, SJL mice exhibited differences in demyelination pattern and severity compared to C57L/6 mice, suggesting a genetic influence on responses to cuprizone intoxication. In addition, the potential therapeutic benefit of estrogen was investigated by administration of 17β-estradiol (E2), at pregnancy levels, to mice during cuprizone intoxication. Interestingly, E2 was effective in partially reducing oligodendrocyte loss and demyelination. This protection was accompanied by a delay in microglia accumulation as well as expression of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) and the growth factor insulin-like growth factor -1 (IGF-1). These studies indicate that estrogen signaling represents an attractive avenue for future studies into therapy of demyelinating disease.

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