PDGF and FGF2 pathways regulate distinct oligodendrocyte lineage responses in experimental demyelination with spontaneous remyelination

Joshua C. Murtie; Yong-Xing Zhou; Tuan Q. Le; Adam C. Vana; Regina C. Armstrong

Neurobiology of Disease (Jun 2005)

PDGF and FGF2 pathways regulate distinct oligodendrocyte lineage responses in experimental demyelination with spontaneous remyelination

Joshua C. Murtie,
Yong-Xing Zhou,
Tuan Q. Le,
Adam C. Vana,
Regina C. Armstrong

Affiliations

Joshua C. Murtie: Program in Molecular and Cell Biology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
Yong-Xing Zhou: Department of Anatomy, Physiology, Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
Tuan Q. Le: Department of Anatomy, Physiology, Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
Adam C. Vana: Program in Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
Regina C. Armstrong: Program in Molecular and Cell Biology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; Department of Anatomy, Physiology, Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; Program in Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; Corresponding author. Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814-4799, USA. Fax: +1 301 295 1715.

Journal volume & issue: Vol. 19, no. 1
pp. 171 – 182

Abstract

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Repair of myelin damage in the adult CNS requires oligodendrocyte progenitor (OP) proliferation and subsequent differentiation into remyelinating oligodendrocytes. Platelet-derived growth factor (PDGF) and fibroblast growth factor-2 (FGF2) have been predicted to act individually and/or cooperatively to generate remyelinating oligodendrocytes. Analysis of PDGF alpha receptor (PDGFαR) heterozygous (+/−) mice indicates that PDGFαR expression modulates oligodendrocyte density in non-lesioned adult CNS. Analysis of cuprizone demyelination and recovery in PDGFαR+/− mice, FGF2 knockout (−/−) mice, and PDGFαR+/− FGF2−/− mice demonstrated that:( 1) OP proliferation and oligodendrocyte regeneration is impaired in PDGFαR heterozygotes, (2) PDGFαR+/− and FGF2−/− deletions do not act cooperatively to impair OP amplification, (3) oligodendrocyte differentiation is more frequent in FGF2−/− mice, and (4) FGF2 deletion in combination with the PDGFαR+/− genotype rescues impaired oligodendrocyte regeneration of PDGFαR heterozygotes. These findings demonstrate distinct roles for PDGF and FGF2 in vivo in the context of a demyelinating disease with spontaneous remyelination.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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Abstract

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