Different effects of constitutive and induced microbiota modulation on microglia in a mouse model of Alzheimer’s disease
Open accessAbstract
It was recently revealed that gut microbiota promote amyloid-beta (Aβ) burden in mouse models of Alzheimer’s disease (AD). However, the underlying mechanisms when using either germ-free (GF) housing conditions or treatments with antibiotics (ABX) remained unknown. In this study, we show that GF and ABX-treated 5x familial AD (5xFAD) mice developed attenuated hippocampal Aβ pathology and associated neuronal loss, and thereby delayed disease-related memory deficits. While Aβ production remained unaffected in both GF and ABX-treated 5xFAD mice, we noticed in GF 5xFAD mice enhanced microglial Aβ uptake at early stages of the disease compared to ABX-treated 5xFAD mice. Furthermore, RNA-sequencing of hippocampal microglia from SPF, GF and ABX-treated 5xFAD mice revealed distinct microbiota-dependent gene expression profiles associated with phagocytosis and altered microglial activation states. Taken together, we observed that constitutive or induced microbiota modulation in 5xFAD mice differentially controls microglial Aβ clearance mechanisms preventing neurodegeneration and cognitive deficits.
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The gut microbiota is required for microglial activation in 5xFAD mice.
“Similarly, the gut microbiota is required for microglial activation in 5xFAD mice.203–205”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [205]
GF mice and mice treated with antibiotics exhibit attenuated phenotypes in AD and MS models.
“Moreover, GF mice and mice treated with antibiotics exhibited attenuated phenotypes in AD and MS models56,57”
From Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype (2023) · cites this paper as [56]
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Gut Microbes: The Gut Brain Connection
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- Authors
- Mezö, C., Dokalis, N., Mossad, O., Staszewski, O., Neuber, J., Yilmaz, B., Schnepf, D., de Agüero, M. G., Ganal-Vonarburg, S. C., Macpherson, A. J., Meyer-Luehmann, M., Staeheli, P., Blank, T., Prinz, M., & Erny, D.
- Affiliations
- University of Freiburg (DE)
- University of Bern (CH)
- Corresponding author
- Erny, Daniel
- ORCID
- Venue
- Acta Neuropathologica Communications
- Published
- 2020-07-29
- Volume
- 8
- Issue
- 1
- Pages
- 119-119
- ISSN
- 2051-5960 (ISSN-L)
- PMC
- PMC7389451
- OpenAlex
- W3046110242
- Cited by
- 120
- References
- 65
- Citations by year
- 2026: 8 · 2025: 20 · 2024: 24 · 2023: 22 · 2022: 21 · 2021: 23 · 2020: 2
- FWCI
- 10.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Acta Neuropathologica Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft (SFB/TRR167, SFB 992, SFB1160, Reinhart Koselleck Grant)
- Berta-Ottenstein-Programme
- Dr. Kübler-Chicken-Stiftung (1027095701)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- gut microbiota, Alzheimer's disease, microglia, amyloid-beta clearance, antibiotic therapy, 5xFAD mice, hippocampus, memory impairment, neurodegeneration, phagocytosis, microglial activation, gene expression profiling
- MeSH terms
- Gastrointestinal Microbiome, Alzheimer Disease, Animals, Anti-Bacterial Agents, Disease Models, Animal, Germ-Free Life, Hippocampus, Humans, Male, Amyloid beta-Protein Precursor, Microglia, Mice
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