Liu Ruicun, Luo Boyu, Yan Honglu, Lin Qing, Liu Wei, Hao Xiaowei, Huang Shuai, Luo Zhenjun, Liu Tuoyu, Li Jinyu, Shi Zhiyuan, Liu Songzuo, Yuan Qing, Teng Yue
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
National Key Laboratory of Underwater Acoustic Technology, Harbin Engineering University, Harbin, 150001, China.
Sci China Life Sci. 2025 Mar 7. doi: 10.1007/s11427-024-2798-3.
Sound pollution (noise) is an increasing environmental concern, particularly associated with neurological and neurobehavioral abnormalities. However, the molecular mechanisms underlying noise-induced neural damage remain unclear. In this study, we conducted transcriptional profiling of zebrafish to investigate the mechanisms underlying acoustic stimulation (1,000 Hz, 130 dB). RNA sequencing and subsequent experiments revealed that TRPV1 is an important mediator of noise-induced neural damage in HuC(elavl3)-GFP transgenic zebrafish. The results demonstrated that inhibiting TRPV1 significantly mitigated noise-induced neural damage in zebrafish with trpv1 gene RNAi and in mice with Trpv1 knockout (Trpv1). Specifically, TRPV1 antagonism significantly reduced neural damage in zebrafish and mice under noise exposure. Furthermore, activated TRPV1 could induce endoplasmic reticulum stress, leading to apoptosis and resulting in neural damage in mice and HEK293T cells. The findings of this study not only enhance our understanding of the molecular mechanisms underlying sound-induced neural damage but also highlight a novel target for drug intervention.
声音污染（噪音）日益引起环境关注，尤其与神经和神经行为异常有关。然而，噪音诱导神经损伤的分子机制仍不清楚。在本研究中，我们对斑马鱼进行转录谱分析，以探究声刺激（1000赫兹，130分贝）的潜在机制。RNA测序及后续实验表明，TRPV1是HuC（elavl3）-GFP转基因斑马鱼中噪音诱导神经损伤的重要介质。结果显示，用trpv1基因RNAi处理斑马鱼以及敲除小鼠的Trpv1基因（Trpv1）后，抑制TRPV1可显著减轻噪音诱导的神经损伤。具体而言，TRPV1拮抗剂可显著减少噪音暴露下斑马鱼和小鼠的神经损伤。此外，激活的TRPV1可诱导内质网应激，导致细胞凋亡，进而造成小鼠和HEK293T细胞的神经损伤。本研究结果不仅增进了我们对声音诱导神经损伤分子机制的理解，还突出了一个药物干预的新靶点。
