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

The identification of new pathways governing myelination provides innovative avenues for remyelination. Liver X receptors (LXRs) a and beta are nuclear receptors activated by oxysterols that originated from the oxidation of cholesterol. They are crucial for cholesterol homeostasis, a major lipid con... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America June 16, 2015, Vol.112(24), pp.7587-7592
Main Author: Meffre, Delphine
Other Authors: Shackleford, Ghjuvan'Ghjacumu , Hichor, Mehdi , Gorgievski, Victor , Tzavara, Eleni T , Trousson, Amalia , Ghoumari, Abdel M , Deboux, Cyrille , Nait Oumesmar, Brahim , Liere, Philippe , Schumacher, Michael , Baulieu, Etienne-Emile , Charbonnier, Frédéric , Grenier, Julien , Massaad, Charbel
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1424951112
Link: http://search.proquest.com/docview/1689843157/?pq-origsite=primo
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title: Liver X receptors alpha and beta promote myelination and remyelination in the cerebellum.
format: Article
creator:
  • Meffre, Delphine
  • Shackleford, Ghjuvan'Ghjacumu
  • Hichor, Mehdi
  • Gorgievski, Victor
  • Tzavara, Eleni T
  • Trousson, Amalia
  • Ghoumari, Abdel M
  • Deboux, Cyrille
  • Nait Oumesmar, Brahim
  • Liere, Philippe
  • Schumacher, Michael
  • Baulieu, Etienne-Emile
  • Charbonnier, Frédéric
  • Grenier, Julien
  • Massaad, Charbel
subjects:
  • Animals–Drug Effects
  • Cell Differentiation–Cytology
  • Cerebellum–Drug Effects
  • Cholesterol–Physiology
  • Gene Expression Regulation–Metabolism
  • Homeostasis–Drug Effects
  • Hydrocarbons, Fluorinated–Pharmacology
  • Hydroxycholesterols–Pharmacology
  • Liver X Receptors–Drug Effects
  • Male–Genetics
  • Mice–Physiology
  • Mice, Knockout–Cytology
  • Myelin Sheath–Drug Effects
  • Oligodendroglia–Metabolism
  • Organ Culture Techniques–Agonists
  • Orphan Nuclear Receptors–Deficiency
  • Promoter Regions, Genetic–Physiology
  • Psychomotor Performance–Drug Effects
  • RNA, Messenger–Physiology
  • Spatial Learning–Genetics
  • Sulfonamides–Metabolism
  • Sulfonamides–Drug Effects
  • Sulfonamides–Physiology
  • Sulfonamides–Pharmacology
  • Hydrocarbons, Fluorinated
  • Hydroxycholesterols
  • Liver X Receptors
  • Nr1h3 Protein, Mouse
  • Orphan Nuclear Receptors
  • RNA, Messenger
  • Sulfonamides
  • To-901317
  • 25-Hydroxycholesterol
  • Cholesterol
  • Lxr Alpha and Beta
  • Cerebellum
  • Myelination
  • Oligodendrocytes
  • Oxysterols
ispartof: Proceedings of the National Academy of Sciences of the United States of America, June 16, 2015, Vol.112(24), pp.7587-7592
description: The identification of new pathways governing myelination provides innovative avenues for remyelination. Liver X receptors (LXRs) a and beta 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 LXRa/ beta 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.
language: eng
source:
identifier: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1424951112
fulltext: fulltext
issn:
  • 10916490
  • 1091-6490
url: Link


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titleLiver X receptors alpha and beta promote myelination and remyelination in the cerebellum.
creatorMeffre, Delphine ; Shackleford, Ghjuvan'Ghjacumu ; Hichor, Mehdi ; Gorgievski, Victor ; Tzavara, Eleni T ; Trousson, Amalia ; Ghoumari, Abdel M ; Deboux, Cyrille ; Nait Oumesmar, Brahim ; Liere, Philippe ; Schumacher, Michael ; Baulieu, Etienne-Emile ; Charbonnier, Frédéric ; Grenier, Julien ; Massaad, Charbel
contributorMeffre, Delphine (correspondence author) ; Meffre, Delphine (record owner)
ispartofProceedings of the National Academy of Sciences of the United States of America, June 16, 2015, Vol.112(24), pp.7587-7592
identifierE-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1424951112
subjectAnimals–Drug Effects ; Cell Differentiation–Cytology ; Cerebellum–Drug Effects ; Cholesterol–Physiology ; Gene Expression Regulation–Metabolism ; Homeostasis–Drug Effects ; Hydrocarbons, Fluorinated–Pharmacology ; Hydroxycholesterols–Pharmacology ; Liver X Receptors–Drug Effects ; Male–Genetics ; Mice–Physiology ; Mice, Knockout–Cytology ; Myelin Sheath–Drug Effects ; Oligodendroglia–Metabolism ; Organ Culture Techniques–Agonists ; Orphan Nuclear Receptors–Deficiency ; Promoter Regions, Genetic–Physiology ; Psychomotor Performance–Drug Effects ; RNA, Messenger–Physiology ; Spatial Learning–Genetics ; Sulfonamides–Metabolism ; Sulfonamides–Drug Effects ; Sulfonamides–Physiology ; Sulfonamides–Pharmacology ; Hydrocarbons, Fluorinated ; Hydroxycholesterols ; Liver X Receptors ; Nr1h3 Protein, Mouse ; Orphan Nuclear Receptors ; RNA, Messenger ; Sulfonamides ; To-901317 ; 25-Hydroxycholesterol ; Cholesterol ; Lxr Alpha and Beta ; Cerebellum ; Myelination ; Oligodendrocytes ; Oxysterols
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descriptionThe identification of new pathways governing myelination provides innovative avenues for remyelination. Liver X receptors (LXRs) a and beta 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 LXRa/ beta 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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titleLiver X receptors alpha and beta promote myelination and remyelination in the cerebellum.
authorMeffre, Delphine ; Shackleford, Ghjuvan'Ghjacumu ; Hichor, Mehdi ; Gorgievski, Victor ; Tzavara, Eleni T ; Trousson, Amalia ; Ghoumari, Abdel M ; Deboux, Cyrille ; Nait Oumesmar, Brahim ; Liere, Philippe ; Schumacher, Michael ; Baulieu, Etienne-Emile ; Charbonnier, Frédéric ; Grenier, Julien ; Massaad,...
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