PDGF and FGF2 pathways regulate distinct oligodendrocyte lineage responses in experimental demyelination with spontaneous remyelination
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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 (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.
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Impaired oligodendrocyte repopulation in PDGFαR heterozygous knockout mice is caused by a reduced proliferation capacity and overall density of OPC.
“Another study showed an impaired oligodendrocyte repopulation in PDGFαR heterozygous knockout mice, caused by a reduced proliferation capacity and overall density of OPC arguing for an important role of PDGFαR-signaling on OPC proliferation.”
From Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned (2014) · cites this paper as Murtie et al., 2005b
PDGFαR-signaling has an important role in OPC proliferation.
“arguing for an important role of PDGFαR-signaling on OPC proliferation.”
From Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned (2014) · cites this paper as Murtie et al., 2005b
Differentiation of OPC was not altered in PDGFαR+/− mice.
“Differentiation of OPC was, however, not altered in PDGFαR +/− mice (Murtie et al., 2005b).”
From Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned (2014) · cites this paper as Murtie et al., 2005b
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- Authors
- Murtie, J. C., Zhou, Y.-X., Le, T. Q., Vana, A. C., & Armstrong, R. C.
- Affiliations
- Uniformed Services University of the Health Sciences (US)
- Corresponding author
- Armstrong, Regina C.
- ORCID
- Armstrong, Regina C.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 19
- Issue
- 1-2
- Pages
- 171-182
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2021786345
- Cited by
- 157
- References
- 50
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 9 · 2023: 5 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 9 · 2018: 7 · 2017: 3 · 2016: 10 · 2015: 11 · 2014: 14 · 2013: 12 · 2012: 8
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS039293, NS39293)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- platelet-derived growth factor, fibroblast growth factor 2, PDGF receptor alpha, oligodendrocyte precursor cells, remyelination, demyelination, cuprizone, oligodendrocyte differentiation, oligodendrocyte proliferation
- MeSH terms
- Animals, Corpus Callosum, Demyelinating Diseases, Male, Mice, Inbred C57BL, Nerve Fibers, Myelinated, Oligodendroglia, Signal Transduction, Fibroblast Growth Factor 2, Mice, Knockout, Cell Lineage, Receptor, Platelet-Derived Growth Factor alpha, NIH 3T3 Cells, Mice
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