Dietary Cholesterol Promotes Repair of Demyelinated Lesions in the Adult Brain

Nat Commun. 2017 Jan 24;8:14241. doi: 10.1038/ncomms14241.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / pathology
  • Biomarkers / blood
  • Brain / cytology
  • Brain / pathology
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Cholesterol / blood*
  • Cholesterol / metabolism
  • Cholesterol, Dietary / administration & dosage*
  • Cholesterol, Dietary / adverse effects
  • Cuprizone / toxicity
  • Dietary Supplements
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / blood
  • Encephalomyelitis, Autoimmune, Experimental / etiology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / chemically induced
  • Multiple Sclerosis / therapy*
  • Myelin Proteins / biosynthesis*
  • Oligodendroglia / cytology
  • Oligodendroglia / pathology
  • Oligodendroglia / physiology
  • Primary Cell Culture
  • Stem Cells / physiology

Substances

  • Biomarkers
  • Cholesterol, Dietary
  • Myelin Proteins
  • Cuprizone
  • Cholesterol