被膜在代谢性年龄相关性听力损失中起关键作用。

IF 10.8 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Sonal Prasad, Marja Pitkänen, Anders Fridberger
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引用次数: 0

摘要

背景:数百万老年人患有年龄相关性听力损失(ARHL),这是一种耳蜗侧壁分泌钾的细胞经常退化的疾病。这种退化降低了在声音刺激时驱动离子进入感觉细胞的力,这被传统上认为是听力丧失的原因。在这里,我们描述了以前未知的ARHL代谢形式的机制。方法:采用荧光光谱和活细胞成像技术,观察侧壁功能障碍对听力器官及其附属结构的影响。对人类颞骨样本的研究证实了关键的发现。结果:侧壁功能障碍导致内耳钙水平下降,这种变化在背毡膜中最为明显,背毡膜是将声刺激传递到感觉细胞立体纤毛的附属结构。这种钙的消耗使感觉细胞失去了一种必需的离子。此外,被膜从立体纤毛上脱落,显著削弱了它们对声音的反应能力。整个听觉器官的持续收缩进一步降低了声诱发反应。解释:这些发现确定了被膜是代谢性ARHL的关键因素,在开发更好的诊断工具或治疗方法时需要考虑到这一点。资助:瑞典研究委员会资助2017-06092和2022-00548,瑞典大脑基金会资助FO2023-0171,美国国立卫生研究院资助R01DC000141-44。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The tectorial membrane has a critical role in metabolic age-related hearing loss.

Background: Millions of older adults have age-related hearing loss (ARHL), a disorder where potassium-secreting cells in the cochlea's lateral wall often degenerate. The degeneration reduces the force that drives ions into the sensory cells during sound stimulation, which is traditionally thought to explain the loss of hearing. Here we describe previously unknown mechanisms underlying this metabolic form of ARHL.

Methods: Fluorescence spectroscopy and live-cell imaging was used in Dunkin-Hartley guinea pigs of either sex to investigate the effects of lateral wall dysfunction on the hearing organ and its accessory structures. Critical findings were confirmed by studying samples of human temporal bones.

Findings: Lateral wall dysfunction caused calcium levels in the inner ear to decline, a change that was most pronounced in the tectorial membrane, an accessory structure crucial for transmitting acoustic stimuli to sensory cell stereocilia. This calcium depletion deprived the sensory cells of an essential ion. Additionally, the tectorial membrane detached from stereocilia, significantly impairing their ability to respond to sound. Sound-evoked responses were further decreased by sustained contraction of the entire hearing organ.

Interpretation: These findings establish the tectorial membrane as a key factor in metabolic ARHL, which needs to be considered when developing better diagnostic tools or treatments.

Funding: Swedish Research Council grants 2017-06092 and 2022-00548, Swedish Brain foundation grant FO2023-0171 and US National Institutes of Health grant R01DC000141-44.

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来源期刊
EBioMedicine
EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍: eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.
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