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Interruption of the Gut Integrity Contributes to Early Accumulation of Amyloid-β in the Enteric Nervous System in Rats Supplemented with a High-Fat Diet

Zeinab Gawish; Maha Gamal; Dalia Azmy Elberry; Esraa A. Hegazy; Laila Ahmed Rashed; Sara Adel Hosny; Marwa Nagi Mehesen; Asmaa Mohammed ShamsEldeen
Molecular Neurobiology · Vol. 62, Issue 12 · pp. 16472-16488 · 2025

Abstract

Consumption of a high-fat diet (HFD) contributes to numerous chronic illnesses, including neurological disorders and gastrointestinal dysfunction. The study design included four groups, each consisting of six rats: the control group was fed regular chow, while groups 2 (HFD 2W), 3 (HFD 4W), and 4 (HFD 8W) were given a 60% HFD for 2, 4, and 8 weeks, respectively. A significant change in the latency to the platform in the water maze, a decrease in the percentage of successful cycles in the Y-maze, and a reduction in the percentage of time spent with the novel object were observed between the baseline and endpoint results in the HFD 4W and HFD 8W groups; notably, this was not the case in the control and HFD 2W groups. Consistent with the increased duration of HFD intake, marked damage to the cortical pyramidal cells as well as the mucosa of the ileum and colon was recorded. The optical density of amyloid deposition was significantly increased in the myenteric plexus before the cerebral cortex. In conclusion, increasing the duration of 60% HFD consumption was associated with significant deterioration of spatial and working memory, an increase in lipid profile, and amyloid deposition in the enteric nervous system, which began even before the observable involvement of the cerebral cortex. Graphical Abstract

Bibliographic Information

JournalMolecular Neurobiology
PublisherSpringer
Publication Date2025-12-01
Publication Year2025
Volume62
Issue12
Pages16472-16488
Document TypeJournal Article
Print ISSN0893-7648
eISSN1559-1182
DOI10.1007/s12035-025-05261-1

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NARA Access Coverage1987-01-01~Current
Journal Homepagehttps://www.springer.com/journal/12035
Publisher PageOpen Publisher Page
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