Intestinal changes in permeability, tight junction and mucin synthesis in a mouse model of Alzheimer's disease.
Int J Mol Med
; 52(6)2023 12.
Article
em En
| MEDLINE
| ID: mdl-37830152
ABSTRACT
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloidß (Aß) in the brain. The gut/brain axis may serve a role in AD pathogenesis. The present study investigated deposition of Aß 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 blueperiodic acid Schiff staining for goblet cells, immunohistochemistry and immunofluorescence for mucin (MUC)2 and wheat germ agglutin expression, transmission electron microscopy for mucosal ultrastructure, FITClabeled 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 Aß 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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
/
Mucinas
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article