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

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.