Defining the Microglia Response during the Time Course of Chronic Neurodegeneration
Open accessAbstract
Inflammation has been proposed as a major component of neurodegenerative diseases, although the precise role it plays has yet to be defined. We examined the role of key contributors to this inflammatory process, microglia, the major resident immune cell population of the brain, in a prion disease model of chronic neurodegeneration. Initially, we performed an extensive reanalysis of a large study of prion disease, where the transcriptome of mouse brains had been monitored throughout the time course of disease. Our analysis has provided a detailed classification of the disease-associated genes based on cell type of origin and gene function. This revealed that the genes upregulated during disease, regardless of the strain of mouse or prion protein, are expressed predominantly by activated microglia. In order to study the microglia contribution more specifically, we established a mouse model of prion disease in which the 79A murine prion strain was introduced by an intraperitoneal route into BALB/cJFms-EGFP/−mice, which express enhanced green fluorescent protein under the control of the c-fms operon. Samples were taken at time points during disease progression, and histological analysis of the brain and transcriptional analysis of isolated microglia was carried out. The analysis of isolated microglia revealed a disease-specific, highly proinflammatory signature in addition to an upregulation of genes associated with metabolism and respiratory stress. This study strongly supports the growing recognition of the importance of microglia within the prion disease process and identifies the nature of the response through gene expression analysis of isolated microglia. IMPORTANCE Inflammation has been proposed as a major component of neurodegenerative diseases. We have examined the role of key contributors to this inflammatory process, microglia, the major resident immune cell population of the brain, in a murine prion disease model of chronic neurodegeneration. Our study demonstrates that genes upregulated throughout the disease process are expressed predominantly by microglia. A disease-specific, highly proinflammatory signature was observed in addition to an upregulation of genes associated with metabolism and respiratory stress. This study strongly supports the growing recognition of the important contribution of microglia to a chronic neurodegenerative disease process.
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Several proinflammatory cytokines, including TNF α, IL 1α, and C1qa, are upregulated in the brain during the prion disease course.
“Several proinflammatory cytokines are upregulated in the brain during the prion disease course including TNF α, IL 1α, and C1qa [46,69,70,71,72,73].”
From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [71]
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- Authors
- Vincenti, J. E., Murphy, L., Grabert, K., McColl, B. W., Cancellotti, E., Freeman, T. C., & Manson, J. C.
- Affiliations
- Roslin Institute (GB)
- Corresponding author
- Manson, Jean C.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2016-03-15
- Volume
- 90
- Issue
- 6
- Pages
- 3003-3017
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC4810622
- OpenAlex
- W2202503777
- Cited by
- 88
- References
- 100
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 4 · 2023: 2 · 2022: 10 · 2021: 12 · 2020: 14 · 2019: 16 · 2018: 10 · 2017: 6 · 2016: 5
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Virology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/F01693X/1)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- microglia, prion disease, neuroinflammation, chronic neurodegeneration, microglial activation, gene expression profiling, transcriptome, microglia isolation, metabolic stress, respiratory stress, prion protein
- MeSH terms
- Animals, Brain, Chronic Disease, Disease Models, Animal, Female, Immunohistochemistry, Inflammation, Male, Mice, Inbred BALB C, Microscopy, Prion Diseases, Microglia, Neurodegenerative Diseases, Gene Expression Profiling
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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