DIA proteomic analysis revealed the molecular characteristics of aluminum-induced hippocampal injury in rats

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology Pub Date : 2025-10-11 DOI:10.1016/j.jtemb.2025.127779

Congying Liu , Yue Shi , Qian Hu , Yafen Chu , Yue Guo , Chaoran Song , Jingjing Jia , Chanting He

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引用次数: 0

Abstract

Background

Aluminum is widely used in production and daily life due to its excellent properties. However, aluminum can damage neurons and cause cognitive impairment. Therefore, studying the neurotoxic mechanism of aluminum is of great significance.

Objective

This study established a subchronic aluminum exposure model in Sprague Dawley rats and systematically investigated the neurotoxic effects and molecular mechanisms of aluminum.

Methods

The experimental animals were randomly divided into a control group (0.9 % saline) and an aluminum exposure group ﹛20 μmol/kg maltol aluminum [Al(mal)₃]﹜. Both groups were given intraperitoneal injections every other day for 90 days. After the administration, the rats received a series of behavioral tests. Subsequently, the rat hippocampus was subjected to data independent acquisition proteomic sequencing.

Result

Through Morris water maze and electron microscopy analysis of hippocampal tissue, it was confirmed that rats exposed to aluminum exhibited significant learning and memory impairments, accompanied by hippocampal neuron damage. The bioinformatics results showed that 188 differentially expressed proteins were screened out. And aluminum exposure mainly damages mitochondrial function (such as oxidative phosphorylation and ATP synthesis). It is worth noting that pathway enrichment analysis suggests a common pathogenic mechanism between aluminum induced neurotoxicity and Alzheimer's disease.

Conclusion

This study confirms that subchronic aluminum exposure leads to cognitive decline by mediating a large amount of protein expression dysregulation. The core mechanism is to impair mitochondrial energy metabolism and synaptic plasticity.

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DIA蛋白质组学分析揭示了铝诱导大鼠海马损伤的分子特征。

背景：铝因其优异的性能被广泛应用于生产和日常生活中。然而，铝会损害神经元并导致认知障碍。因此，研究铝的神经毒性机制具有重要意义。目的：建立大鼠亚慢性铝暴露模型，系统探讨铝的神经毒性作用及其分子机制。方法：将实验动物随机分为对照组（0.9 %生理盐水）和铝暴露组（20 μmol/kg麦芽糖醇铝[Al(mal)3]}）。两组大鼠每隔一天腹腔注射一次，连续90 d。给药后，老鼠接受了一系列的行为测试。随后，对大鼠海马进行数据独立获取蛋白质组测序。结果：通过Morris水迷宫和海马组织电镜分析，证实铝暴露大鼠表现出明显的学习记忆障碍，并伴有海马神经元损伤。生物信息学结果显示，共筛选出188个差异表达蛋白。而铝暴露主要损害线粒体功能（如氧化磷酸化和ATP合成）。值得注意的是，途径富集分析提示铝诱导的神经毒性与阿尔茨海默病之间存在共同的致病机制。结论：本研究证实亚慢性铝暴露通过介导大量蛋白表达失调导致认知能力下降。其核心机制是损害线粒体能量代谢和突触可塑性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Trace Elements in Medicine and Biology 医学-内分泌学与代谢

CiteScore

6.60

自引率

2.90%

发文量

202

审稿时长

85 days

期刊介绍： The journal provides the reader with a thorough description of theoretical and applied aspects of trace elements in medicine and biology and is devoted to the advancement of scientific knowledge about trace elements and trace element species. Trace elements play essential roles in the maintenance of physiological processes. During the last decades there has been a great deal of scientific investigation about the function and binding of trace elements. The Journal of Trace Elements in Medicine and Biology focuses on the description and dissemination of scientific results concerning the role of trace elements with respect to their mode of action in health and disease and nutritional importance. Progress in the knowledge of the biological role of trace elements depends, however, on advances in trace elements chemistry. Thus the Journal of Trace Elements in Medicine and Biology will include only those papers that base their results on proven analytical methods. Also, we only publish those articles in which the quality assurance regarding the execution of experiments and achievement of results is guaranteed.