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Androgens show sex-dependent differences in myelination in immune and non-immune murine models of CNS demyelination

Author

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  • Amina Zahaf

    (U1195 Inserm, Paris-Saclay University)

  • Abdelmoumen Kassoussi

    (U1195 Inserm, Paris-Saclay University)

  • Tom Hutteau-Hamel

    (UMR996 Inserm, Paris-Saclay University)

  • Amine Mellouk

    (UMR996 Inserm, Paris-Saclay University)

  • Corentine Marie

    (Paris Brain Institute, Sorbonne University)

  • Lida Zoupi

    (The University of Edinburgh, Edinburgh BioQuarter)

  • Foteini Tsouki

    (The University of Edinburgh, Edinburgh BioQuarter)

  • Claudia Mattern

    (M et P Pharma AG)

  • Pierre Bobé

    (UMR996 Inserm, Paris-Saclay University)

  • Michael Schumacher

    (U1195 Inserm, Paris-Saclay University)

  • Anna Williams

    (The University of Edinburgh, Edinburgh BioQuarter)

  • Carlos Parras

    (Paris Brain Institute, Sorbonne University)

  • Elisabeth Traiffort

    (U1195 Inserm, Paris-Saclay University)

Abstract

Neuroprotective, anti-inflammatory, and remyelinating properties of androgens are well-characterized in demyelinated male mice and men suffering from multiple sclerosis. However, androgen effects mediated by the androgen receptor (AR), have been only poorly studied in females who make low androgen levels. Here, we show a predominant microglial AR expression in demyelinated lesions from female mice and women with multiple sclerosis, but virtually undetectable AR expression in lesions from male animals and men with multiple sclerosis. In female mice, androgens and estrogens act in a synergistic way while androgens drive microglia response towards regeneration. Transcriptomic comparisons of demyelinated mouse spinal cords indicate that, regardless of the sex, androgens up-regulate genes related to neuronal function integrity and myelin production. Depending on the sex, androgens down-regulate genes related to the immune system in females and lipid catabolism in males. Thus, androgens are required for proper myelin regeneration in females and therapeutic approaches of demyelinating diseases need to consider male-female differences.

Suggested Citation

  • Amina Zahaf & Abdelmoumen Kassoussi & Tom Hutteau-Hamel & Amine Mellouk & Corentine Marie & Lida Zoupi & Foteini Tsouki & Claudia Mattern & Pierre Bobé & Michael Schumacher & Anna Williams & Carlos Pa, 2023. "Androgens show sex-dependent differences in myelination in immune and non-immune murine models of CNS demyelination," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36846-w
    DOI: 10.1038/s41467-023-36846-w
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    References listed on IDEAS

    as
    1. Meng-Lei Zhu & Pearl Bakhru & Bridget Conley & Jennifer S. Nelson & Meghan Free & Aaron Martin & Joshua Starmer & Elizabeth M. Wilson & Maureen A. Su, 2016. "Sex bias in CNS autoimmune disease mediated by androgen control of autoimmune regulator," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    2. Shane A. Liddelow & Kevin A. Guttenplan & Laura E. Clarke & Frederick C. Bennett & Christopher J. Bohlen & Lucas Schirmer & Mariko L. Bennett & Alexandra E. Münch & Won-Suk Chung & Todd C. Peterson & , 2017. "Neurotoxic reactive astrocytes are induced by activated microglia," Nature, Nature, vol. 541(7638), pages 481-487, January.
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