Skip to Content
MilliporeSigma

Gut microbiota-driven brain Aβ amyloidosis in mice requires microglia.

The Journal of experimental medicine (2021-12-03)
Hemraj B Dodiya, Holly L Lutz, Ian Q Weigle, Priyam Patel, Julia Michalkiewicz, Carlos J Roman-Santiago, Can Martin Zhang, Yingxia Liang, Abhinav Srinath, Xulun Zhang, Jessica Xia, Monica Olszewski, Xiaoqiong Zhang, Matthew John Schipma, Eugene B Chang, Rudolph E Tanzi, Jack A Gilbert, Sangram S Sisodia
ABSTRACT

We previously demonstrated that lifelong antibiotic (ABX) perturbations of the gut microbiome in male APPPS1-21 mice lead to reductions in amyloid β (Aβ) plaque pathology and altered phenotypes of plaque-associated microglia. Here, we show that a short, 7-d treatment of preweaned male mice with high-dose ABX is associated with reductions of Aβ amyloidosis, plaque-localized microglia morphologies, and Aβ-associated degenerative changes at 9 wk of age in male mice only. More importantly, fecal microbiota transplantation (FMT) from transgenic (Tg) or WT male donors into ABX-treated male mice completely restored Aβ amyloidosis, plaque-localized microglia morphologies, and Aβ-associated degenerative changes. Transcriptomic studies revealed significant differences between vehicle versus ABX-treated male mice and FMT from Tg mice into ABX-treated mice largely restored the transcriptome profiles to that of the Tg donor animals. Finally, colony-stimulating factor 1 receptor (CSF1R) inhibitor-mediated depletion of microglia in ABX-treated male mice failed to reduce cerebral Aβ amyloidosis. Thus, microglia play a critical role in driving gut microbiome-mediated alterations of cerebral Aβ deposition.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Amyloid Fibrils OC Antibody, serum, Chemicon®