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  • Multiple sclerosis is an auto-immune, demyelinating and neurodegenerative pathology of the central nervous system (CNS). The early phase of the disease mostly corresponds to a relapsing-remitting form with a succession of demyelinating events, each followed by spontaneous myelin regeneration. Over time, remyelination however eventually fails, which leads to irreversible neurological disabilities. From a clinical point of view, the disease is sexually dimorphic with a three-fold higher prevalence in women and more severe forms occurring at a later age in men. Importantly, any sexual hormone deregulation has been correlated with clinical worsening. Although obviously different, the male and female hormonal environment is not restricted to high androgen levels in males and fluctuating estrogen/progesterone levels in females. Males can indeed convert androgens to estrogens while females synthesize small amounts of androgens. The role of androgens was still unexplored, so we set out to address the question by using pharmacological and genetic approaches in various demyelination models. We show an unexpected and strong up-regulation of the androgen receptor AR in the demyelinated lesions from female mice and MS female patients, the unique involvement of androgens in the response of microglia/macrophages to demyelination in females and a sexual dimorphism characterizing androgen effects in the demyelinated CNS at the molecular level. Our work suggests the use of appropriate doses of androgens in demyelinated females and it uncovers the need for considering the sex-specific AR-mediated control of microglia/macrophage response to demyelination in the therapeutic management of multiple sclerosis.

    Conference Room R229 – Saint-Germain-des-Prés Campus – 45 rue des Saints-Pères, 75006 Paris – March 22nd, 2024 at 11:30 AM