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

• Published in: Neurobiology of disease Vol. 19; no. 1; pp. 171 - 182
• Main Authors: Murtie, Joshua C., Zhou, Yong-Xing, Le, Tuan Q., Vana, Adam C., Armstrong, Regina C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2005; Elsevier
• Subjects: Animals; Cell Lineage - genetics; Cell Lineage - physiology; Corpus Callosum - metabolism; Corpus Callosum - pathology; Cuprizone; Demyelinating disease; Demyelinating Diseases - metabolism; Demyelinating Diseases - pathology; Demyelination; Differentiation; Fibroblast growth factor; Fibroblast Growth Factor 2 - deficiency; Fibroblast Growth Factor 2 - genetics; Fibroblast Growth Factor 2 - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Multiple sclerosis; Nerve Fibers, Myelinated - pathology; Nerve Fibers, Myelinated - physiology; NIH 3T3 Cells; Oligodendrocyte; Oligodendroglia - pathology; Oligodendroglia - physiology; Platelet-derived growth factor; Progenitor; Receptor, Platelet-Derived Growth Factor alpha - deficiency; Receptor, Platelet-Derived Growth Factor alpha - genetics; Receptor, Platelet-Derived Growth Factor alpha - physiology; Remyelination; Signal Transduction - genetics; Signal Transduction - physiology; Demyelinating disease; Fibroblast growth factor; Multiple sclerosis; Platelet-derived growth factor; Oligodendrocyte; Cuprizone; Demyelination; Progenitor; Differentiation; Remyelination
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2004.12.006

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.