Retinoid X receptor gamma signaling accelerates CNS remyelination | Zendy

Jeffrey K. Huang | Zendy; Andrew A. Jarjour | Zendy; Brahim NaitOumesmar | Zendy; Christophe Kerni | Zendy; Anna Williams | Zendy; Wojciech Krężel | Zendy; Hiroyuki Kagechika | Zendy; Julien Bauer | Zendy; Chao Zhao | Zendy; Anne BaronVan Evercooren | Zendy; Pierre Chambon | Zendy; Charles ffrenchConstant | Zendy; Robin J.M. Franklin | Zendy

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Retinoid X receptor gamma signaling accelerates CNS remyelination

Author(s) -

Jeffrey K. Huang,

Andrew A. Jarjour,

Brahim NaitOumesmar,

Christophe Kerni,

Anna Williams,

Wojciech Krężel,

Hiroyuki Kagechika,

Julien Bauer,

Chao Zhao,

Anne BaronVan Evercooren,

Pierre Chambon,

Charles ffrenchConstant,

Robin J.M. Franklin

Publication year - 2010

Publication title -

nature neuroscience

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 13.403

H-Index - 422

eISSN - 1546-1726

pISSN - 1097-6256

DOI - 10.1038/nn.2702

Subject(s) - remyelination , oligodendrocyte , biology , retinoid x receptor , retinoic acid , multiple sclerosis , myelin , neuroscience , microbiology and biotechnology , central nervous system , nuclear receptor , immunology , transcription factor , cell culture , biochemistry , genetics , gene

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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