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Liver X receptors regulate cholesterol homeostasis in oligodendrocytes
Author(s) -
Nelissen Katherine,
Mulder Monique,
Smets Ilse,
Timmermans Silke,
Smeets Karen,
Ameloot Marcel,
Hendriks Jerome J.A.
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22743
Subject(s) - liver x receptor , abca1 , oligodendrocyte , abcg1 , remyelination , biology , oxysterol , npc1 , apolipoprotein e , cholesterol , medicine , endocrinology , nuclear receptor , microbiology and biotechnology , myelin , receptor , transporter , biochemistry , gene , transcription factor , central nervous system , endosome , disease
Abstract Cholesterol synthesis and transport in oligodendrocytes are essential for optimal myelination and remyelination in pathological conditions such as multiple sclerosis. However, little is known about cholesterol homeostasis in the myelin‐forming oligodendrocytes. Liver X receptors (LXRs) are nuclear oxysterol receptors that regulate genes involved in cholesterol homeostasis and may therefore play an important role in de‐ and remyelination. We investigated whether LXRs regulate cholesterol homeostasis in oligodendrocytes. mRNA expression of genes encoding LXR‐α and LXR‐β and their target genes (ABCA1, ABCG1, ABCG4, apoE, and LDLR) was detected in oligodendrocytes derived from both neonatal and adult rats using quantitative real‐time PCR. The expression of LXR‐β and several target genes was increased during oligodendrocyte differentiation. We further demonstrated that treatment of primary neonatal rat oligodendrocytes with the synthetic LXR agonist T0901317 induced the expression of several established LXR target genes, including ABCA1, ABCG1, apoE, and LDLR. Treatment of oligodendrocytes with T0901317 resulted in an enhanced cholesterol efflux in the presence of apolipoprotein A‐I or high‐density lipoprotein particles. These data show that LXRs are involved in regulating cholesterol homeostasis in oligodendrocytes. © 2011 Wiley Periodicals, Inc.