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 (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.
Murtie
Joshua C
JC
Program in Molecular and Cell Biology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA.
Zhou
Yong-Xing
YX
Le
Tuan Q
TQ
Vana
Adam C
AC
Armstrong
Regina C
RC
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*
D016222:Fibroblast Growth Factor 2; D020796:Receptor, Platelet-Derived Growth Factor alpha