title: Remyelination is altered by bone morphogenic protein signaling in demyelinated lesions.
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.
authors: Centre for Neuroscience, University of Melbourne, Parkville, Victoria 3010, Australia.
authors: Jennifer K
authors: JK
authors: Sabo
authors: Tim D
authors: TD
authors: Aumann
authors: Daniel
authors: D
authors: Merlo
authors: Trevor J
authors: TJ
authors: Kilpatrick
authors: Holly S
authors: HS
authors: Cate
mesh_terms: D000818:Animals; D000963:Antimetabolites; D001253:Astrocytes / Q000502:physiology; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D001973:Bromodeoxyuridine; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D002452:Cell Count; D002614:Chelating Agents; D003337:Corpus Callosum / Q000473:pathology; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology; D009836:Oligodendroglia / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology; D000099176:Noggin Protein
chemical_list: D000963:Antimetabolites; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D001973:Bromodeoxyuridine; D002352:Carrier Proteins; D002614:Chelating Agents; D003471:Cuprizone; D000099176:Noggin Protein