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Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2016

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

Bartosz Bielecki
  • Fonction : Auteur
Claudia Mattern
  • Fonction : Auteur
Abdel M. Ghoumari
  • Fonction : Auteur
Sumaira Javaid
  • Fonction : Auteur
Kaja Smietanka
  • Fonction : Auteur
Charly Abi Ghanem
  • Fonction : Auteur
M. Said Ghandour
  • Fonction : Auteur
Etienne-Emile Baulieu
  • Fonction : Auteur
Robin J. M. Franklin
  • Fonction : Auteur
Michael Schumacher
  • Fonction : Auteur
Elisabeth Traiffort
  • Fonction : Auteur

Résumé

Lost myelin can be replaced after injury or during demyelinating diseases in a regenerative process called remyelination. In the central nervous system (CNS), the myelin sheaths, which protect axons and allow the fast propagation of electrical impulses, are produced by oligodendrocytes. The abundance and widespread distribution of oligodendrocyte progenitors (OPs) within the adult CNS account for this remarkable regenerative potential. Here, we report a key role for the male gonad, testosterone, and androgen receptor (AR) in CNS remyelination. After lysolecithin-induced demyelination of the male mouse ventral spinal cord white matter, the recruitment of glial fibrillary acidic protein-expressing astrocytes was compromised in the absence of testes and testosterone signaling via AR. Concomitantly, the differentiation of OPs into oligodendrocytes forming myelin basic protein (MBP)(+) and proteolipid protein-positive myelin was impaired. Instead, in the absence of astrocytes, axons were remyelinated by protein zero (P0)(+) and peripheral myelin protein 22-kDa (PMP22)(+) myelin, normally only produced by Schwann cells in the peripheral nervous system. Thus, testosterone favors astrocyte recruitment and spontaneous oligodendrocyte-mediated remyelination. This finding may have important implications for demyelinating diseases, psychiatric disorders, and cognitive aging. The testosterone dependency of CNS oligodendrocyte remyelination may have roots in the evolutionary history of the AR, because the receptor has evolved from an ancestral 3-keto-steroid receptor through gene duplication at the time when myelin appeared in jawed vertebrates.

Dates et versions

hal-01542821 , version 1 (20-06-2017)

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Citer

Bartosz Bielecki, Claudia Mattern, Abdel M. Ghoumari, Sumaira Javaid, Kaja Smietanka, et al.. Unexpected central role of the androgen receptor in the spontaneous regeneration of myelin. Proceedings of the National Academy of Sciences of the United States of America, 2016, 113 (51), pp.14829-14834. ⟨10.1073/pnas.1614826113⟩. ⟨hal-01542821⟩
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