Cited by 122Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsGut microbiota and health

Different effects of constitutive and induced microbiota modulation on microglia in a mouse model of Alzheimer’s disease

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Mezö, Charlotte, Dokalis, Nikolaos, Mossad, Omar, Staszewski, Ori, Neuber, Jana, Yilmaz, Bahtiyar, Schnepf, Daniel, de Agüero, Mercedes Gomez +7 more·2020·Acta Neuropathologica Communications

Abstract

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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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
Venue
Acta Neuropathologica Communications
Published
2020-07-29
Volume
8
Issue
1
Pages
119-119
ISSN
2051-5960 (ISSN-L)
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
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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