Enhanced M-CSF/CSF1R Signaling Closely Associates with PrPSc Accumulation in the Scrapie-Infected Cell Line and the Brains of Scrapie-Infected Experimental Rodents
Abstract
Activation and proliferation of microglia are one of the hallmarks of prion disease and is usually accompanied by increased levels of various cytokines and chemokines. Our previous study demonstrated that the level of brain macrophage colony-stimulating factor (M-CSF) was abnormally elevated during prion infection, but its association with PrP Sc is not completely clear. In this study, colocalization of the increased M-CSF with accumulated PrP Sc was observed by IHC with serial brain sections. Reliable molecular interaction between total PrP and M-CSF was observed in the brain of 263 K-infected hamsters and in cultured prion-infected cell line. Immunofluorescent assays showed that morphological colocalization of M-CSF with neurons and microglia, but not with astrocytes in brains of scrapie-infected animals. The transcriptional and expressing levels of CSF1R were also significantly increased in prion-infected cell line and mice, and colocalization of CSF1R with neurons and microglia was observed in the brains of prion-infected mouse models. Removal of PrP Sc replication by resveratrol in SMB-S15 cells induced limited reductions of cellular levels of M-CSF and CSF1R. In addition, we found that the level of IL-34, another ligand of CSF1R, did not change significantly after prion infection, but its distribution on the cell types in the brains shifted from neurons in healthy mice to the proliferated astrocytes and microglia in scrapie-infected mice. Our data demonstrate activation of M-CSF/IL-34/CSF1R signaling in the microenvironment of prion infection, strongly indicating its vital role in the pathophysiology of prions. It provides solid scientific evidence for the therapeutic potential of inhibiting M-CSF/CSF1R signaling in prion diseases.
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M-CSF/CSF1R signaling is upregulated in prion infection.
“Interestingly, novel data have also shown that M-CSF/CSF1R signaling is upregulated in prion infection [57].”
From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [57]
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Loss of Homeostatic Microglia Signature in Prion Diseases
Wang, Y., Hartmann, K., Thies, E., Mohammadi, B., Altmeppen, H., Sepulveda-Falla, D., Glatzel, M., & Krasemann, S. (2022) · Cells · doi:10.3390/cells11192948 · Cited by 12 · see citing works
“Interestingly, novel data have also shown that MCSF/CSF1R signaling is upregulated in prion infection [57].”
Background
- Authors
- Xia, Y., Chen, C., Chen, J., Hu, C., Yang, W., Wang, L., Liu, L., Gao, L.-P., Wu, Y.-Z., Chen, D.-D., Shi, Q., Chen, Z.-B., & Dong, X.-P.
- Affiliations
- Chinese Center For Disease Control and Prevention (CN)
- Corresponding author
- Chen, Cao
- Dong, Xiao-Ping
- ORCID
- Venue
- Molecular Neurobiology
- Published
- 2022-08-15
- Volume
- 59
- Issue
- 10
- Pages
- 6534-6551
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W4291624791
- Cited by
- 7
- References
- 55
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 2 · 2022: 1
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- SKLID Development Grant (2021SKLID504, 2019SKLID401, 2019SKLID603)
- National Natural Science Foundation of China (81772197, 81630062, 81401670)
- Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (2018RC330004)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- prion disease, scrapie, macrophage colony-stimulating factor, CSF1R, IL-34, prion protein accumulation, microglial activation, astrocytes, resveratrol, prion replication, prion disease therapy
- MeSH terms
- Animals, Brain, Cell Line, Cricetinae, Pregnancy Proteins, Prions, Rodentia, Scrapie, Macrophage Colony-Stimulating Factor, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, Prion Diseases, PrPSc Proteins, Mice
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