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

Amina Zahaf, Abdelmoumen Kassoussi, Tom Hutteau-Hamel, Amine Mellouk, Corentine Marie, Lida Zoupi, Foteini Tsouki, Claudia Mattern, Pierre Bobé, Michael Schumacher, Anna Williams, Carlos Parras and Elisabeth Traiffort ()
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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

Nature Communications, 2023, vol. 14, issue 1, 1-21

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36846-w

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