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

Mezö, Charlotte; Dokalis, Nikolaos; Mossad, Omar; Staszewski, Ori; Neuber, Jana; Yilmaz, Bahtiyar; Schnepf, Daniel; Gomez de Agüero, Mercedes; Ganal-Vonarburg, Stephanie C.; Macpherson, Andrew J.; Meyer-Luehmann, Melanie; Staeheli, Peter; Blank, Thomas; Prinz, Marco; Erny, Daniel (2020). Different effects of constitutive and induced microbiota modulation on microglia in a mouse model of Alzheimer's disease. Acta neuropathologica communications, 8(1), p. 119. BioMed Central 10.1186/s40478-020-00988-5

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

UniBE Contributor:

Yilmaz, Bahtiyar; Gomez de Agüero Tamargo, Maria de la Mercedes; Ganal-Vonarburg, Stephanie Christine and Macpherson, Andrew

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2051-5960

Publisher:

BioMed Central

Language:

English

Submitter:

Rahel Fuhrer

Date Deposited:

16 Dec 2020 17:09

Last Modified:

20 Dec 2020 02:56

Publisher DOI:

10.1186/s40478-020-00988-5

PubMed ID:

32727612

Uncontrolled Keywords:

Alzheimer’s disease Antibiotics Germ-free Gut microbiota Microglia

BORIS DOI:

10.7892/boris.148425

URI:

https://boris.unibe.ch/id/eprint/148425

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