The Affiliated Guangzhou Twelfth People's Hospital, Guangzhou Medical University.
Key Laboratory of Occupational Environment and Health, Guangzhou Twelfth People's Hospital.
Environ Health Prev Med. 2024;29:50. doi: 10.1265/ehpm.24-00126.
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.
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.
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.
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.
慢性噪声暴露对公众健康构成了显著威胁，引起了人们对其对大脑影响的关注。铁死亡与多种与大脑相关的疾病有关。然而，铁死亡在慢性噪声对大脑影响中的作用仍不清楚。本研究旨在探讨慢性噪声暴露对大脑的影响，并阐明其潜在机制。
构建并验证了大鼠慢性噪声诱导认知障碍模型。采用 Western blot 和免疫组织化学法测定大鼠海马的病理状态和铁死亡水平。采用生物信息学方法研究慢性噪声暴露与基因之间的相互关系。采用孟德尔随机化（MR）分析分析遗传关系。采用 Cytoscape 预测上游分子和药物靶点。
体内实验表明，慢性噪声暴露可引起大鼠海马阿尔茨海默病（AD）样神经病理改变和认知障碍。此外，还定量测定了铁死亡和脂质过氧化的蛋白标志物，以阐明潜在机制。随后，对氧化应激和铁死亡相关差异表达基因（DEGs）进行了功能富集和 PPI 网络分析。此外，还鉴定了 8 个具有诊断意义的基因。在 MR 分析中，维甲酸受体应答基因 2（Rarres2）基因与 AD 呈负遗传关系。
慢性噪声暴露可通过铁死亡诱导 AD 样神经病理改变和认知障碍。MR 分析的结果表明，Rarres2 基因可能是 AD 的保护因素。该基因可能位于铁死亡的上游，可作为预防和治疗慢性噪声诱导认知障碍的靶点。
