title: Dietary cholesterol promotes repair of demyelinated lesions in the adult brain.
abstract: Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes.
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany.
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Berghoff
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Gerndt
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Winchenbach
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany.
authors.forename: Sina K
authors.initials: SK
authors.lastname: Stumpf
authors.affiliation: Institute of Neuroimmunology and Institute for Multiple Sclerosis Research, University Medical Centre Göttingen, Waldweg 33, 37073 Göttingen, Germany.
authors.forename: Leon
authors.initials: L
authors.lastname: Hosang
authors.affiliation: Institute of Neuroimmunology and Institute for Multiple Sclerosis Research, University Medical Centre Göttingen, Waldweg 33, 37073 Göttingen, Germany.
authors.forename: Francesca
authors.initials: F
authors.lastname: Odoardi
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany.
authors.forename: Torben
authors.initials: T
authors.lastname: Ruhwedel
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Böhler
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany.
authors.forename: Benoit
authors.initials: B
authors.lastname: Barrette
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany.|Department of Neuropathology, University Medical Center, Georg-August-University, Robert Koch Str. 40, 37075 Göttingen, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Stassart
authors.affiliation: Department of Clinical Neurophysiology, Georg-August University, Robert Koch Str. 40, 37075 Göttingen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Liebetanz
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany.
authors.forename: Payam
authors.initials: P
authors.lastname: Dibaj
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany.|Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Wilhelmsplatz 1, 37073 Göttingen, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Möbius
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany.|Applied Neurobiology Group, Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G12-8TA, UK.
authors.forename: Julia M
authors.identifier: 0000-0002-3869-0962
authors.initials: JM
authors.lastname: Edgar
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany.
authors.forename: Gesine
authors.initials: G
authors.lastname: Saher
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000166:cytology / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage* / Q000009:adverse effects; D003471:Cuprizone / Q000633:toxicity; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000209:etiology / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000097:blood / Q000139:chemically induced / Q000628:therapy*; D009185:Myelin Proteins / Q000096:biosynthesis*; D009836:Oligodendroglia / Q000166:cytology / Q000473:pathology / Q000502:physiology; D061251:Primary Cell Culture; D013234:Stem Cells / Q000502:physiology
chemical_list: D015415:Biomarkers; D002791:Cholesterol, Dietary; D009185:Myelin Proteins; D003471:Cuprizone; D002784:Cholesterol