Modulation of bone morphogenic protein signalling alters numbers of astrocytes and oligodendroglia in the subventricular zone during cuprizone-induced demyelination

Holly S. Cate, Jennifer K. Sabo, Daniel Merlo, Dennis Kemper, Tim D. Aumann, Julien Robinson, Toby D. Merson, Ben Emery, Victoria M. Perreau, Trevor J. Kilpatrick

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

The adult subventricular zone (SVZ) is a potential source of precursor cells to replace neural cells lost during demyelination. To better understand the molecular events that regulate neural precursor cell responsiveness in this context we undertook a microarray and quantitative PCR based analysis of genes expressed within the SVZ during cuprizone-induced demyelination. We identified an up-regulation of the genes encoding bone morphogenic protein 4 (BMP4) and its receptors. Immunohistochemistry confirmed an increase in BMP4 protein levels and also showed an increase in phosphorylated SMAD 1/5/8, a key component of BMP4 signalling, during demyelination. In vitro analysis revealed that neural precursor cells isolated from demyelinated animals, as well as those treated with BMP4, produce more astrocytes. Similarly, there were increased numbers of astrocytes in vivo within the SVZ during demyelination. Intraventricular infusion of Noggin, an endogenous antagonist of BMP4, during cuprizone-induced demyelination reduced pSMAD1/5/8, decreased astrocyte numbers and increased oligodendrocyte numbers in the SVZ. Our results suggest that lineage commitment of SVZ neural precursor cells is altered during demyelination and that BMP signalling plays a role in this process.

Original languageEnglish (US)
Pages (from-to)11-22
Number of pages12
JournalJournal of neurochemistry
Volume115
Issue number1
DOIs
StatePublished - Oct 2010

Keywords

  • Noggin
  • astrocyte
  • bone morphogenic protein
  • demyelination
  • oligodendrocyte
  • subventricular zone

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Modulation of bone morphogenic protein signalling alters numbers of astrocytes and oligodendroglia in the subventricular zone during cuprizone-induced demyelination'. Together they form a unique fingerprint.

Cite this