Remyelination is altered by bone morphogenic protein signaling in demyelinated lesions

J Neurosci. 2011 Mar 23;31(12):4504-10. doi: 10.1523/JNEUROSCI.5859-10.2011.

Abstract

Remyelination of the CNS involves the regeneration of mature oligodendrocytes by endogenous oligodendrocyte progenitor cells (OPCs). Previous studies have shown that bone morphogenic proteins (BMPs) inhibit the production of oligodendrocytes in the healthy CNS. However, there is currently no information on the influence of BMP signaling in vivo within demyelinated lesions of the brain or on subsequent remyelination. Here, we determine a role for BMP signaling in modulating oligodendrogliogenesis and remyelination in the brain following cuprizone-induced demyelination. We identified that BMP signaling is active in oligodendroglia and astrocytes within the demyelinated corpus callosum. Intraventricular infusion of BMP4 into the brains of mice during demyelination increased the proliferation of OPCs and, to a lesser extent, microglia and astrocytes in the corpus callosum. In contrast, infusion of Noggin, an extracellular antagonist of BMP4, increased the density of mature oligodendrocytes in the remyelinating corpus callosum. Additional evidence from myelin staining and electron microscopy indicates there is an increase in remyelinated axons in the corpus callosum of Noggin-infused mice. Thus, inhibition of endogenous BMP signaling during demyelination promotes mature oligodendrocyte regeneration and remyelination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites
  • Astrocytes / physiology
  • Bone Morphogenetic Protein 4 / pharmacology
  • Bone Morphogenetic Proteins / physiology*
  • Bromodeoxyuridine
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology
  • Cell Count
  • Chelating Agents
  • Corpus Callosum / pathology
  • Cuprizone
  • Demyelinating Diseases / chemically induced
  • Demyelinating Diseases / pathology*
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron
  • Myelin Sheath / physiology*
  • Neuroglia / physiology
  • Oligodendroglia / physiology
  • Signal Transduction / physiology*
  • Stem Cells / physiology

Substances

  • Antimetabolites
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Carrier Proteins
  • Chelating Agents
  • noggin protein
  • Cuprizone
  • Bromodeoxyuridine