Effects of high-fructose diet on hippocampal neurometabolites and anxiety and depression-like behaviors in mice

doi:10.16098/j.issn.0529-1356.2025.04.001

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Acta Anatomica Sinica ›› 2025, Vol. 56 ›› Issue (4) : 381-388. DOI: 10.16098/j.issn.0529-1356.2025.04.001

Effects of high-fructose diet on hippocampal neurometabolites and anxiety and depression-like behaviors in mice

ZHANG Shan-shan¹ LIU Ying² ZHANG Yu-wen² WANG He² LI Wen-sheng^1,3,4* LIU Qiong^1,3*

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Abstract

Objective To investigate the effects of short-term and long-term high-fructose diets on hippocampal neurometabolites and anxiety and depression-like behaviors in mice, revealing the potential mechanisms of high-fructose diets in mood disorders and providing a experimental basis for the prevention and treatment of related diseases. Methods C57BL/6J male mice were randomly divided into two groups, control group (standard diet, n=10) and experimental group (high-fructose diet, n=10). Four weeks (short-term) and eight weeks (long-term) later, each group of mice was examined for body weight and fasting blood glucose, and neurometabolites levels in the hippocampus were detected by hydrogen proton magnetic resonance spectroscopy(1H-MRS), followed by the open-field test, the forced-swimming test, and the tail-suspension test to evaluate anxiety-like and depression-like behaviors. Results High fructose diet for 4 weeks elevated glutamate levels and reduced glutathione and myo-inositol levels in mice, accompanied by shortened immobility time in the forced swim test. High fructose diet for 8 weeks not only led to abnormalities in body weight and glucose metabolism but also caused a reversal decrease in hippocampal glutamate levels and induced significant anxiety-like behaviors, and the decrease in hippocampal glutamate levels showed a significant negative correlation with the enhancement of anxiety-like behaviors. Conclusion Altered hippocampal glutamate levels may be a key contributing factor to the anxiety-like behaviors induced by long-term high-fructose diet.

Key words

High-fructose diet

/ Anxiety / Hippocampus / Neurometabolity / Hydrogen proton magnetic resonance spectroscopy / Mouse

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ZHANG Shan-shan LIU Ying ZHANG Yu-wen WANG He LI Wen-sheng LIU Qiong. Effects of high-fructose diet on hippocampal neurometabolites and anxiety and depression-like behaviors in mice[J]. Acta Anatomica Sinica. 2025, 56(4): 381-388 https://doi.org/10.16098/j.issn.0529-1356.2025.04.001

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