小胶质细胞
ABX试验
微生物群
淀粉样变性
转基因小鼠
转录组
生物
转基因
淀粉样蛋白(真菌学)
病理
免疫学
医学
炎症
基因表达
生物信息学
基因
统计
数学
生物化学
作者
Hemraj B. Dodiya,Holly L. Lutz,Ian Q. Weigle,Priyam Patel,Julia Michalkiewicz,Carlos J. Roman-Santiago,Can Zhang,Yingxia Liang,Abhinav Srinath,Xulun Zhang,J. Xia,Monica Olszewski,Xiaoqiong Zhang,Matthew J. Schipma,Eugene B. Chang,Rudolph E. Tanzi,Jack A. Gilbert,Sangram S. Sisodia
摘要
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.
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