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

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

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Acta neuropathologica communications. - 8, 1 (2020) , 119, ISSN: 2051-5960

Klassifikation und Themen

• Schlagwort: Darmflora ; Antibiotikum ; Sterilität ; Mikroglia ; Alzheimerkrankheit

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2020
• Urheber: 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-Lühmann, Melanie ; Stäheli, Peter ; Blank, Thomas ; Prinz, Marco ; Erny, Daniel

Weitere Informationen

• DOI: 10.1186/s40478-020-00988-5
• URN: urn:nbn:de:bsz:25-freidok-1669300
• Rechteinformation: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 14.08.2025, 10:50 MESZ