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Liver X receptors alpha and beta promote myelination and remyelination in the cerebellum.

Proceedings of the National Academy of Sciences of the United States of America (2015-05-30)
Delphine Meffre, Ghjuvan'Ghjacumu Shackleford, Mehdi Hichor, Victor Gorgievski, Eleni T Tzavara, Amalia Trousson, Abdel M Ghoumari, Cyrille Deboux, Brahim Nait Oumesmar, Philippe Liere, Michael Schumacher, Etienne-Emile Baulieu, Frédéric Charbonnier, Julien Grenier, Charbel Massaad

The identification of new pathways governing myelination provides innovative avenues for remyelination. Liver X receptors (LXRs) α and β are nuclear receptors activated by oxysterols that originated from the oxidation of cholesterol. They are crucial for cholesterol homeostasis, a major lipid constituent of myelin sheaths that are formed by oligodendrocytes. However, the role of LXRs in myelin generation and maintenance is poorly understood. Here, we show that LXRs are involved in myelination and remyelination processes. LXRs and their ligands are present in oligodendrocytes. We found that mice invalidated for LXRs exhibit altered motor coordination and spatial learning, thinner myelin sheaths, and reduced myelin gene expression. Conversely, activation of LXRs by either 25-hydroxycholesterol or synthetic TO901317 stimulates myelin gene expression at the promoter, mRNA, and protein levels, directly implicating LXRα/β in the transcriptional control of myelin gene expression. Interestingly, activation of LXRs also promotes oligodendroglial cell maturation and remyelination after lysolecithin-induced demyelination of organotypic cerebellar slice cultures. Together, our findings represent a conceptual advance in the transcriptional control of myelin gene expression and strongly support a new role of LXRs as positive modulators in central (re)myelination processes.

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Methylene Blue solution, for microscopy, concentrate according to Ehrlich, concentrated, aqueous solution
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