Unexpected central role of the androgen receptor in the spontaneous regeneration of myelin

Significance Myelin allows the rapid conduction of electrical signals and provides axons with metabolic support. It appeared relatively late in evolution in hinge-jawed vertebrates and concomitantly with the emergence of the androgen receptor (AR), hinting at a specific role for androgens in myelination. Here, we show that after demyelination of the central nervous system (CNS), the male gonad, testosterone, and AR favor astrocyte recruitment and myelin regeneration by oligodendrocytes. In their absence, astrocytes remain sparse and peripheral-type remyelination, classically associated with Schwann cells, is predominantly detected. These findings reveal a novel role of androgen signaling in CNS myelin formation and glial cell communication, with possible implications for demyelinating, psychiatric, and age-related disorders.