噪音会诱导细胞间Ca2+信号波和听力中的未折叠蛋白质反应
bioRxiv : the preprint server for biology
|June 19, 2024
概括
暴露于大声噪音会破坏耳朵中的平衡和内质网膜压力,导致听力损失. 针对这些途径可能为噪音引起的听力损失提供新的治疗方法.
科学领域:
- 耳声学排放的排放.
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
背景情况:
- 获得性听力损失通常是由暴露于大噪声引起的.
- 细胞内膜网膜应激和破坏的平衡与噪音引起的听力损失有关.
- 现有有限的方法可以研究成熟的,暴露于噪音的小鼠耳朵中的动态.
研究的目的:
- 为了研究平衡与噪音暴露小鼠的压力路径之间的关联.
- 分析噪声暴露对尾细胞通路的剂量依赖影响.
- 探索噪音引起的听力损失的潜在治疗点.
主要方法:
- 利用一种基因编码的指标小鼠模型 (GcAMP在头发和支持细胞中的表达).
- 进行活成像和展开蛋白质反应 (UPR) 基因表达分析.
- 暴露在8周大的小鼠噪音水平导致耳突触 (98 dB SPL) 或永久性听力损失 (106 dB SPL).
主要成果:
- 在暴露于噪音后,UPR的激活是立即的,并且取决于剂量.
- 只有在106dB的噪声暴露后,亲细胞亡路径才得到上调.
- 噪音暴露在毛发细胞中重新激活了静止的过渡物和支持细胞中的细胞间波,暴露106dB导致了更持久的活性.
结论:
- 在耳细胞中,暴露于噪音,UPR激活和改变的平衡之间显示出强烈的,剂量依赖的联系.
- 成熟囊中的重新激活的动态表明噪音诱导损伤的潜在机制.
- 建议针对噪音引起的听力损失的新治疗方法的UPR和平衡途径.
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