{"title":"Chronic noise exposure induces Alzheimer's disease-like neuropathology and cognitive impairment via ferroptosis in rat hippocampus.","authors":"Jialao Ma, Jinwei Zhang, Zejin Ou, Yixian Ren, Kangyong Wu, Yifan Zhang, Siran Chen, Zhi Wang","doi":"10.1265/ehpm.24-00126","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Chronic noise exposure poses a remarkable public health concern, drawing attention to its impacts on the brain. Ferroptosis is involved in several brain-related diseases. However, the role of ferroptosis in the effects of chronic noise on the brain remains elusive. This study aimed to investigate the effects of chronic noise exposure on the brain and elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>A chronic noise-induced cognitive impairment model in rats was constructed and validated. The pathological state and ferroptosis level of the rat hippocampus were determined using Western blotting and immunohistochemistry. Bioinformatics was employed to investigate the interrelationship between chronic noise exposure and genes. Genetic relationships were analyzed using Mendelian randomization (MR) analysis. Cytoscape was employed for the prediction of upstream molecular and drug targets.</p><p><strong>Results: </strong>In vivo experiments revealed that chronic noise exposure could induce Alzheimer's disease (AD)-like neuropathological changes in rat hippocampus and cognitive impairment. Moreover, protein markers indicative of ferroptosis and levels of lipid peroxidation were quantified to elucidate underlying mechanisms. Thereafter, oxidative stress- and ferroptosis-related differentially expressed genes (DEGs) underwent functional enrichment and PPI network analyses. Additionally, 8 genes with diagnostic significance were identified. In MR analysis, retinoic acid receptor responder 2 (Rarres2) gene exhibited a negative genetic relationship with AD.</p><p><strong>Conclusions: </strong>Chronic noise exposure could induce AD-like neuropathological changes and cognitive impairment via ferroptosis. The results of MR analysis indicated that Rarres2 gene may act as a protective factor in AD. This gene may be upstream of ferroptosis and serve as a target for the prevention and treatment of chronic noise-induced cognitive impairment.</p>","PeriodicalId":11707,"journal":{"name":"Environmental Health and Preventive Medicine","volume":"29 ","pages":"50"},"PeriodicalIF":4.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446637/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Environmental Health and Preventive Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1265/ehpm.24-00126","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Chronic noise exposure poses a remarkable public health concern, drawing attention to its impacts on the brain. Ferroptosis is involved in several brain-related diseases. However, the role of ferroptosis in the effects of chronic noise on the brain remains elusive. This study aimed to investigate the effects of chronic noise exposure on the brain and elucidate the underlying mechanisms.
Methods: A chronic noise-induced cognitive impairment model in rats was constructed and validated. The pathological state and ferroptosis level of the rat hippocampus were determined using Western blotting and immunohistochemistry. Bioinformatics was employed to investigate the interrelationship between chronic noise exposure and genes. Genetic relationships were analyzed using Mendelian randomization (MR) analysis. Cytoscape was employed for the prediction of upstream molecular and drug targets.
Results: In vivo experiments revealed that chronic noise exposure could induce Alzheimer's disease (AD)-like neuropathological changes in rat hippocampus and cognitive impairment. Moreover, protein markers indicative of ferroptosis and levels of lipid peroxidation were quantified to elucidate underlying mechanisms. Thereafter, oxidative stress- and ferroptosis-related differentially expressed genes (DEGs) underwent functional enrichment and PPI network analyses. Additionally, 8 genes with diagnostic significance were identified. In MR analysis, retinoic acid receptor responder 2 (Rarres2) gene exhibited a negative genetic relationship with AD.
Conclusions: Chronic noise exposure could induce AD-like neuropathological changes and cognitive impairment via ferroptosis. The results of MR analysis indicated that Rarres2 gene may act as a protective factor in AD. This gene may be upstream of ferroptosis and serve as a target for the prevention and treatment of chronic noise-induced cognitive impairment.
背景：长期暴露于噪音环境是一个令人关注的公共健康问题，它对大脑的影响引起了人们的注意。铁蜕变与多种脑相关疾病有关。然而，铁蜕变在慢性噪声对大脑的影响中所起的作用仍然难以捉摸。本研究旨在调查慢性噪声暴露对大脑的影响，并阐明其潜在机制：方法：构建并验证了慢性噪声诱导的大鼠认知障碍模型。方法：构建了慢性噪声诱导的大鼠认知障碍模型并对其进行了验证，采用 Western 印迹和免疫组化方法测定了大鼠海马的病理状态和铁蛋白沉积水平。利用生物信息学研究了慢性噪声暴露与基因之间的相互关系。利用孟德尔随机化（MR）分析法对基因关系进行了分析。采用 Cytoscape 预测上游分子和药物靶点：体内实验表明，长期暴露于噪声可诱发大鼠海马发生类似阿尔茨海默病（AD）的神经病理变化，并导致认知障碍。此外，实验还量化了指示铁变态反应的蛋白质标记物和脂质过氧化水平，以阐明其潜在机制。随后，对氧化应激和铁中毒相关的差异表达基因（DEGs）进行了功能富集和PPI网络分析。此外，还发现了 8 个具有诊断意义的基因。在MR分析中，视黄酸受体应答器2（Rarres2）基因与AD呈负遗传关系：结论：慢性噪声暴露可通过铁氧化诱发类似 AD 的神经病理变化和认知障碍。MR分析结果表明，Rarres2基因可能是AD的保护因子。该基因可能处于铁蛋白沉积的上游，是预防和治疗慢性噪声诱导的认知障碍的靶点。
期刊介绍：
The official journal of the Japanese Society for Hygiene, Environmental Health and Preventive Medicine (EHPM) brings a comprehensive approach to prevention and environmental health related to medical, biological, molecular biological, genetic, physical, psychosocial, chemical, and other environmental factors.
Environmental Health and Preventive Medicine features definitive studies on human health sciences and provides comprehensive and unique information to a worldwide readership.
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