Macrophage-depletion induced impairment of experimental CNS remyelination is associated with a reduced oligodendrocyte progenitor cell response and altered growth factor expression
Open accessAbstract
Although macrophages are mediators of CNS demyelination, they are also implicated in remyelination. To examine the role of macrophages in CNS remyelination, adult rats were depleted of monocytes using clodronate liposomes and demyelination induced in the spinal cord white matter using lysolecithin. In situ hybridization for scavenger receptor-B and myelin basic protein (MBP) revealed a transiently impaired macrophage response associated with delayed remyelination in liposome-treated animals. Macrophage reduction corresponded with delayed recruitment of PDGFRalpha+ oligodendrocyte progenitor cells (OPCs), which preceded changes in myelin phagocytosis, indicating a macrophage effect on OPCs independent of myelin debris clearance. Macrophage-depletion induced changes in the mRNA expression of insulin-like growth factor-1 and transforming growth factor beta1, but not platelet-derived growth factor-A and fibroblast growth factor-2. These data suggest that the macrophage response to toxin-induced demyelination influences the growth factor environment, thereby affecting the behavior of OPCs and hence the efficiency of remyelination.
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Microglia/macrophages exhibit regenerative properties through the phagocytosis of myelin debris and secretion of growth/neurotrophic factors.
“they also exhibit regenerative properties through the phagocytosis of myelin debris3, 4 and secretion of growth/neurotrophic factors5.”
From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [5]
The delayed OPC recruitment after macrophage depletion is linked to an altered growth factor expression in macrophage-depleted animals.
“The authors linked this phenomenon to an altered growth factor expression in macrophage-depleted animals (Kotter et al., 2001, 2005).”
From Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned (2014) · cites this paper as Kotter et al., 2005
Depletion of macrophages via clodronate-liposomes prior/after lysolecithin-induced demyelination delays OPC recruitment.
“Kotter and colleagues, who demonstrated a delayed OPC recruitment after the depletion of macrophages via exposure of mice to clodronate-liposomes prior/after lysolecithin-induced demyelination.”
From Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned (2014) · cites this paper as Kotter et al., 2005
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- Authors
- Kotter, M. R., Zhao, C., van Rooijen, N., & Franklin, R. J. M.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Franklin, Robin J.M.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 18
- Issue
- 1
- Pages
- 166-175
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2061771806
- Cited by
- 331
- References
- 6
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 20 · 2023: 15 · 2022: 9 · 2021: 20 · 2020: 19 · 2019: 23 · 2018: 13 · 2017: 23 · 2016: 10 · 2015: 20 · 2014: 20 · 2013: 16 · 2012: 19
- FWCI
- 6.92
- 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
- Multiple Sclerosis Society
- Austrian Science Fund
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- macrophages, oligodendrocyte precursor cells, macrophage depletion, clodronate liposomes, spinal cord white matter, PDGFRA, myelin phagocytosis, insulin-like growth factor I, TGF-β1, PDGF-A, fibroblast growth factor 2, growth factor expression, demyelination
- MeSH terms
- Animals, Central Nervous System, Demyelinating Diseases, Disease Models, Animal, Myelin Basic Protein, Female, Growth Substances, Macrophages, Myelin Sheath, Nerve Regeneration, Oligodendroglia, Phagocytosis, Receptors, Immunologic, RNA, Stem Cells, Down-Regulation, Rats, Sprague-Dawley, Receptor, Platelet-Derived Growth Factor alpha, Receptors, Scavenger, Rats
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