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Retinoid X receptor gamma signaling accelerates CNS remyelination

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Huang, Jeffrey | Jarjour, Andrew | Nait Oumesmar, Brahim | Kerninon, Christophe | Williams, Anna | Krezel, Wojciech | Kagechika, Hiroyuki | Bauer, Julien | Zhao, Chao | Evercooren, Anne Baron-Van | Chambon, Pierre | Ffrench-Constant, Charles | Franklin, Robin

Edité par CCSD ; Nature Publishing Group -

International audience. The molecular basis of CNS myelin regeneration (remyelination) is poorly understood. We generated a comprehensive transcriptional profile of the separate stages of spontaneous remyelination that follow focal demyelination in the rat CNS and found that transcripts that encode the retinoid acid receptor RXR-γ were differentially expressed during remyelination. Cells of the oligodendrocyte lineage expressed RXR-γ in rat tissues that were undergoing remyelination and in active and remyelinated multiple sclerosis lesions. Knockdown of RXR-γ by RNA interference or RXR-specific antagonists severely inhibited oligodendrocyte differentiation in culture. In mice that lacked RXR-γ, adult oligodendrocyte precursor cells efficiently repopulated lesions after demyelination, but showed delayed differentiation into mature oligodendrocytes. Administration of the RXR agonist 9-cis-retinoic acid to demyelinated cerebellar slice cultures and to aged rats after demyelination caused an increase in remyelinated axons. Our results indicate that RXR-γ is a positive regulator of endogenous oligodendrocyte precursor cell differentiation and remyelination and might be a pharmacological target for regenerative therapy in the CNS.

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