肠道菌群
生物
过剩3
葡萄糖转运蛋白
过剩1
共域化
过剩4
肠-脑轴
胶质纤维酸性蛋白
多巴胺能
内分泌学
内科学
多巴胺
生物化学
细胞生物学
免疫学
医学
免疫组织化学
胰岛素
作者
Ling Hao,Lijing Wang,Mengwei Ju,Wuwen Feng,Zhengchen Guo,Xuejing Sun,Rong Xiao
标识
DOI:10.1016/j.biopha.2023.115649
摘要
Brain glucose hypometabolism is a significant manifestation of Alzheimer's disease (AD). 27-hydroxycholesterol (27-OHC) and the gut microbiota have been recognized as factors possibly influencing the pathogenesis of AD. This study aimed to investigate the link between 27-OHC, the gut microbiota, and brain glucose uptake in AD. Here, 6-month-old male C57BL/6 J mice were treated with sterile water or antibiotic cocktails, with or without 27-OHC and/or 27-OHC synthetic enzyme CYP27A1 inhibitor anastrozole (ANS). The gut microbiota, brain glucose uptake levels, and memory ability were measured. We observed that 27-OHC altered microbiota composition, damaged brain tissue structures, decreased the 2-deoxy-2-[18 F] fluorodeoxyglucose (18F-FDG) uptake value, downregulated the gene expression of glucose transporter type 4 (GLUT4), reduced the colocalization of GLUT1/glial fibrillary acidic protein (GFAP) in the hippocampus, and impaired spatial memory. ANS reversed the effects of 27-OHC. The antibiotic-treated mice did not exhibit similar results after 27-OHC treatment. This study reveals a potential molecular mechanism wherein 27-OHC-induced memory impairment might be linked to reduced brain glucose uptake, mediated by the gut microbiota.
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