PLX121082

GSE154428: Different effects of constitutive and induced microbiota modulation on microglia in a mouse model of Alzheimers disease

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

It was recently revealed that gut microbiota promote amyloid-beta (A) burden in mouse models of Alzheimers 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 A pathology and associated neuronal loss, and thereby delayed disease-related memory deficits. While Ab production remained unaffected in both GF and ABX-treated 5xFAD mice, we noticed in GF 5xFAD mice enhanced microglial A 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 A clearance mechanisms preventing neurodegeneration and cognitive deficits. SOURCE: Ori Staszewski (ori.staszewski@uniklinik-freiburg.de) - University Medical Center Freiburg