"Intestinal changes in permeability, tight junction and mucin synthesis in a mouse model of Alzheimer's disease"

作者全名："He, Jing; Liu, Yuanjie; Li, Junhua; Zhao, Yueyang; Jiang, Hanxiao; Luo, Shifang; He, Guiqiong"

作者地址："[He, Jing; Liu, Yuanjie; Li, Junhua; Zhao, Yueyang; Luo, Shifang; He, Guiqiong] Chongqing Med Univ, Inst Neurosci, Sch Basic Med Sci, 1 Yi Xue Yuan Rd, Chongqing 400016, Peoples R China; [He, Jing; Liu, Yuanjie; Li, Junhua; Zhao, Yueyang; Luo, Shifang; He, Guiqiong] Chongqing Med Univ, Sch Basic Med Sci, Dept Anat, Chongqing 400016, Peoples R China; [Jiang, Hanxiao] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurol, Chongqing 400010, Peoples R China"

通信作者："Luo, SF; He, GQ (通讯作者)，Chongqing Med Univ, Inst Neurosci, Sch Basic Med Sci, 1 Yi Xue Yuan Rd, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001099298900001

JCR分区：Q1

影响因子：5.4

年份：2023

卷号：52

期号：6

开始页：　

结束页：　

文献类型：Article

关键词：Alzheimer's disease; amyloid-beta; intestinal barrier; goblet cell; MUC2; Notch signaling pathway

摘要："Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-beta (A beta) in the brain. The gut/brain axis may serve a role in AD pathogenesis. The present study investigated deposition of A beta in the intestinal epithelium and its potential effects on intestinal barrier function in a transgenic mouse model of AD. To investigate alterations in the structure and functionality of the intestinal mucosal barrier in AD model mice, hematoxylin and eosin staining for Paneth cell count, Alcian blue-periodic acid Schiff staining for goblet cells, immunohistochemistry and immunofluorescence for mucin (MUC)2 and wheat germ agglutin expression, transmission electron microscopy for mucosal ultrastructure, FITC-labeled dextran assay for intestinal permeability, quantitative PCR for goblet cell precursor expression and western blot analysis for tight junction proteins, MUC2 and inflammatory cytokine detection were performed. The results showed that AD model mice exhibited excessive A beta deposition in the intestinal epithelium, which was accompanied by increased intestinal permeability, inflammatory changes and decreased expression of tight junction proteins. These alterations in the intestinal barrier led to an increased proliferation of goblet and Paneth cells and increased mucus synthesis. Dysfunction of gut barrier occurs in AD and may contribute to its etiology. Future therapeutic strategies to reverse AD pathology may involve early manipulation of gut physiology and its microbiota."

基金机构：Not applicable.

基金资助正文：Not applicable.