Impact of a High-Fat Fructose Diet From Early Life to Young Adulthood on Spatial Memory Deficits in Male Rats: Assessments Using the Barnes Maze and Morris Water Maze Publisher Pubmed

Summary: Could 4-PBA protect memory from a high-fat, high-fructose diet? A rat study found reduced brain inflammation and improved spatial memory measures after treatment. #BrainHealth #Nutrition

Izadi M S ; Salimi M ; Eskandari F ; Zardooz H
Source: Physiology and Behavior Published:2026

Abstract

Background Chronic intake of a high-fat-fructose (HFF) diet may result in oxidative stress and inflammation, ultimately leading to cognitive impairments. To assess potential spatial memory deficits resulting from HFF diet consumption from birth to young adulthood and the impact of 4-phenylbutyric acid (4-PBA) treatment, two spatial memory assessment tests were utilized: the Barnes maze (BM) and the Morris water maze (MWM) tests. Methods After delivery, dams and their pups were randomly assigned to either the control (Ctrl) or the HFF diet group. After weaning, male pups were subdivided into the four groups based on the diet and treatment: Ctrl-DMSO, Ctrl-4-PBA, HFF-DMSO, and HFF-4-PBA. They continued their respective diets for five weeks, followed by a ten-day drug injection period. Behavioral tests, including BM and MWM tests, were performed on the sixth and seventh days of drug treatment, respectively. Finally, plasma corticosterone levels, as well as hippocampal levels of interleukin-1beta (IL-1β) and oxidative stress markers, were measured. Results Early life to young adulthood consumption of HFF diet caused hippocampal IL-1β and malondialdehyde (MDA) contents, alongside a decrease in glutathione (GSH) level. These alterations were accompanied by memory impairment, decreased time spent in the target area, and increased latency to first in the HFF-DMSO group. 4-PBA administration improved the adverse changes in HFF-fed rats. Based on the behavioral findings, the BM appeared to be more sensitive than the MWM in identifying spatial memory impairments. Conclusion Overall, a prolonged HFF diet consumption led to inflammation and oxidative stress in the hippocampus, which was associated with memory impairments in young adult male rats. The findings indicate that 4-PBA may represent a promising therapeutic approach to mitigate the negative biochemical and behavioral effects of such dietary exposure. Furthermore, the BM test is recommended as a useful tool for assessing potential spatial memory deficits in dietary intervention studies. © 2026 Elsevier Inc.