Systemic Inflammation Accelerates Changes in Microglial and Synaptic Markers in an Experimental Model of Chronic Neurodegeneration
Open accessAbstract
Bacterial infections are a common cause of morbidity and mortality in the elderly, and particularly in individuals with a neurodegenerative disease. Experimental models of neurodegeneration have shown that LPS-induced systemic inflammation increases neuronal damage, a process thought to be mediated by activation of “primed” microglia. The effects of a real systemic bacterial infection on the innate immune cells in the brain and neuronal networks are less well described, and therefore, in this study we use the ME7 prion model to investigate the alterations in microglia activation and phenotype and synaptic markers in response to a low grade, live bacterial infection. Mice with or without a pre-existing ME7 prion-induced neurodegenerative disease were given a single systemic injection of live Salmonella typhimurium at early or mid-stage of disease progression. Immune activation markers CD11b and MHCII and pro-inflammatory cytokines were analyzed 4 weeks post-infection. Systemic infection with S. typhimurium resulted in an exaggerated inflammatory response when compared to ME7 prion mice treated with saline. These changes to inflammatory markers were most pronounced at mid-stage disease. Analysis of synaptic markers in ME7 prion mice revealed a significant reduction of genes that are associated with early response in synaptic plasticity, extracellular matrix structure and post-synaptic density, but no further reduction following systemic infection. In contrast, analysis of activity-related neuronal receptors involved in development of learning and memory, such as Grm1 and Grin2a, showed a significant decrease in response to systemic bacterial challenge. These changes were observed early in the disease progression and associated with reduced burrowing activity. The exaggerated innate immune activation and altered expression of genes linked to synaptic plasticity may contribute to the onset and/or progression of neurodegeneration.
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The region-specific increase in microglia numbers during the course of prion disease has been shown with several mouse-adapted prion strains and may be aggravated by systemic infection.
“The region-specific increase in microglia numbers during the course of a prion disease had already been shown with several mouse adapted prion strains [45,46,47] and may be aggravated by systemic infection [48,49].”
From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [48]
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References 58 · Cited by 24
- Authors
- Chouhan, J. K., Püntener, U., Booth, S. G., & Teeling, J. L.
- Affiliations
- University of Southampton (GB)
- Corresponding author
- Teeling, Jessica L.
- Venue
- Frontiers in Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2022-01-04
- Volume
- 15
- Pages
- 760721-760721
- ISSN
- 1662-453X (ISSN-L)
- PMC
- PMC8764443
- OpenAlex
- W4206127822
- Cited by
- 24
- References
- 58
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 3
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Wellcome Trust
- Medical Research Council (MR/N017897)
- 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
- systemic inflammation, microglial activation, synaptic plasticity, Salmonella typhimurium infection, bacterial infection, innate immune activation, CD11b, MHC class II, inflammatory cytokines, synaptic markers, postsynaptic density, extracellular matrix, metabotropic glutamate receptor 1, burrowing behavior
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