CXCR4 promotes differentiation of oligodendrocyte progenitors and remyelination

Jigisha R. Patel, Erin E. McCandless, Denise Dorsey, Robyn S. Klein

Research output: Contribution to journalArticlepeer-review

176 Scopus citations

Abstract

Multiple sclerosis is a neurodegenerative disease characterized by episodes of autoimmune attack of oligodendrocytes leading to demyelination and progressive functional deficits. Because many patients exhibit functional recovery in between demyelinating episodes, understanding mechanisms responsible for repair of damaged myelin is critical for developing therapies that promote remyelination and prevent disease progression. The chemokine CXCL12 is a developmental molecule known to orchestrate the migration, proliferation, and differentiation of neuronal precursor cells within the developing CNS. Although studies suggest a role for CXCL12 in oligodendroglia ontogeny in vitro, no studies have investigated the role of CXCL12 in remyelination in vivo in the adult CNS. Using an experimental murine model of demyelination mediated by the copper chelator cuprizone, we evaluated the expression of CXCL12 and its receptor, CXCR4, within the demyelinating and remyelinating corpus callosum (CC). CXCL12 was significantly up-regulated within activated astrocytes and microglia in the CC during demyelination, as were numbers of CXCR4+ NG2+ oligodendrocyte precursor cells (OPCs). Loss of CXCR4 signaling via either pharmacological blockade or in vivo RNA silencing led to decreased OPCs maturation and failure to remyelinate. These data indicate that CXCR4 activation, by promoting the differentiation of OPCs into oligodendrocytes, is critical for remyelination of the injured adult CNS.

Original languageEnglish
Pages (from-to)11062-11067
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number24
DOIs
StatePublished - Jun 15 2010

Keywords

  • CXCL12
  • Central nervous system
  • Chemokine
  • Cuprizone

Fingerprint

Dive into the research topics of 'CXCR4 promotes differentiation of oligodendrocyte progenitors and remyelination'. Together they form a unique fingerprint.

Cite this