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Retinoid X Receptor activation reverses the age-related deficiency in myelin debris phagocytosis and enhances remyelination

ABSTRACT: The efficiency of central nervous system (CNS) remyelination declines with age. This is in part due to an age-associated decline in the phagocytic removal of myelin debris, which contains inhibitors of oligodendrocyte progenitor cell differentiation. In this study we show that expression of genes involved in the retinoid X receptor (RXR) pathway are decreased with aging in myelin-phagocytosing cells. Loss of RXR function in young macrophages mimics aging by delaying remyelination after experimentally-induced demyelination, while RXR agonists partially restore myelin debris phagocytosis in aged macrophages. The FDA-approved RXR agonist bexarotene, when used in concentrations achievable in human subjects, caused a reversion of the gene expression profile in aging human monocytes to a more youthful profile. These results reveal the RXR pathway as a positive regulator of myelin debris clearance and a key player in the age-related decline in remyelination that may be targeted by available or newly-developed therapeutics.

ORGANISM(S): Homo sapiens

PROVIDER: GSE66988 | GEO | 2015/11/04

SECONDARY ACCESSION(S): PRJNA278645

REPOSITORIES: GEO

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Retinoid X Receptor activation reverses the age-related deficiency in myelin debris phagocytosis and enhances remyelination

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