Journal article
Different effects of constitutive and induced microbiota modulation on microglia in a mouse model of Alzheimer's disease.
- Mezö C Institute of Neuropathology, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany.
- Dokalis N Institute of Neuropathology, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany.
- Mossad O Institute of Neuropathology, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany.
- Staszewski O Institute of Neuropathology, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany.
- Neuber J Institute of Neuropathology, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany.
- Yilmaz B Maurice E. Müller Laboratories, Department for Biomedical Research (DBMR), University Clinic of Visceral Surgery and Medicine, Inselspital, University of Bern, Bern, Switzerland.
- Schnepf D Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany.
- de Agüero MG Maurice E. Müller Laboratories, Department for Biomedical Research (DBMR), University Clinic of Visceral Surgery and Medicine, Inselspital, University of Bern, Bern, Switzerland.
- Ganal-Vonarburg SC Maurice E. Müller Laboratories, Department for Biomedical Research (DBMR), University Clinic of Visceral Surgery and Medicine, Inselspital, University of Bern, Bern, Switzerland.
- Macpherson AJ Maurice E. Müller Laboratories, Department for Biomedical Research (DBMR), University Clinic of Visceral Surgery and Medicine, Inselspital, University of Bern, Bern, Switzerland.
- Meyer-Luehmann M Department of Neurology, Medical Center University of Freiburg, Freiburg, Germany.
- Staeheli P Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany.
- Blank T Institute of Neuropathology, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany.
- Prinz M Institute of Neuropathology, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany.
- Erny D Institute of Neuropathology, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany. daniel.erny@uniklinik-freiburg.de.
- 2020-07-31
Published in:
- Acta neuropathologica communications. - 2020
English
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.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.1186/s40478-020-00988-5
- PMID 32727612
- Persistent URL
- https://folia.unifr.ch/global/documents/222565
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