title: PDGF and FGF2 pathways regulate distinct oligodendrocyte lineage responses in experimental demyelination with spontaneous remyelination.
abstract: 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 (PDGF alpha R) heterozygous (+/-) mice indicates that PDGF alpha R expression modulates oligodendrocyte density in non-lesioned adult CNS. Analysis of cuprizone demyelination and recovery in PDGF alpha R+/- mice, FGF2 knockout (-/-) mice, and PDGF alpha R+/- FGF2-/- mice demonstrated that: (1) OP proliferation and oligodendrocyte regeneration is impaired in PDGF alpha R heterozygotes, (2) PDGF alpha R+/- 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 PDGF alpha R+/- genotype rescues impaired oligodendrocyte regeneration of PDGF alpha R heterozygotes. These findings demonstrate distinct roles for PDGF and FGF2 in vivo in the context of a demyelinating disease with spontaneous remyelination.
authors.affiliation: Program in Molecular and Cell Biology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Murtie
authors.forename: Yong-Xing
authors.initials: YX
authors.lastname: Zhou
authors.forename: Tuan Q
authors.initials: TQ
authors.lastname: Le
authors.forename: Adam C
authors.initials: AC
authors.lastname: Vana
authors.forename: Regina C
authors.initials: RC
authors.lastname: Armstrong
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology; D003711:Demyelinating Diseases / Q000378:metabolism* / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology*; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D016222:Fibroblast Growth Factor 2; D020796:Receptor, Platelet-Derived Growth Factor alpha