Retinoid X receptor gamma signaling accelerates CNS remyelination

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

Research output: Contribution to journalArticlepeer-review

368 Citations (SciVal)

Abstract

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.

Original languageEnglish
Pages (from-to)45-55
Number of pages11
JournalNature Neuroscience
Volume14
Issue number1
DOIs
Publication statusPublished - 5 Dec 2011

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