Sleep disturbance and dysregulation of circadian clock machinery in sudden sensorineural hearing loss

Abstract

Background

The cochlea contains a robust biological clock associated with auditory function, exhibiting diurnal sensitivity to noise or ototoxicity

Objectives

We examined the relationship between disrupted circadian rhythm and altered expression of circadian clock genes in patients with sudden sensorineural hearing loss (SSNHL) and explored whether the circadian clock genes serve as prognostic biomarkers.

Material and Methods

Twelve patients with SSNHL were enrolled study group. Twelve people with normal hearing were enrolled voluntarily for comparison. Audiological evaluation was performed to evaluate hearing thresholds. Korean version of the Pittsburgh Sleep Quality Index Questionnaire was performed to evaluate sleep quality and patterns. Circadian clock genes including for PERI, PER2, PER3, CRYI, CRY2, CLOCK, ARNTL, CSNKIE, and TIMELESS expression in blood were evaluated using real-time quantitative PCR method.

Results

Compared with healthy controls without hearing loss, most of the circadian clock genes were markedly downregulated, coupled with low sleep quality and disturbing patterns, in patients with SSNHL. Intriguingly, a weak correlation between hearing improvement following steroid treatment and altered levels of circadian clock genes was observed.

Conclusions and Significance

This study provides an additional basis for the relevance of disrupted circadian rhythm to SSNHL and suggests a possible prognostic biomarker for SSNHL treatment.

Chinese abstract

背景：耳蜗带有与听觉功能相关的稳固的生物钟, 表现出对噪音或耳毒性的日敏感性。

目标：我们研究了突发感音神经性听力损失（SSNHL）患者的昼夜节律紊乱与昼夜生物钟基因的表达改变之间的关系, 并探索了生物钟基因是否可以作为预后生物标志物。

材料和方法：12 名 SSNHL 患者被纳入研究组。十二个听力正常的自愿参与者作为对照。 进行听力学评估以评估听力阈值。 进行了韩国版匹兹堡睡眠质量指数问卷调查, 以评估睡眠质量和模式。 使用实时定量PCR方法, 评估血液中的昼夜节律时钟基因, 包括 PERI、PER2、PER3、CRYI、CRY2、CLOCK、ARNTL、CSNKIE 和 TIMELESS 表达。

结果：与没有听力损失的健康对照组相比, SSNHL患者的大多数生物钟基因显著下调, 并伴有睡眠质量低和睡眠打断模式。 有趣的是, 我们观察到类固醇治疗后的听力改善与生物钟基因水平的改变之间存在微弱的相关性。

结论和意义：这项研究为中断的昼夜节律对于SSNHL的相关性提供了更多的基础, 并为 SSNHL 治疗提出了一个可能的预后生物标志物。

Keywords:

• Circadian rhythm
• circadian clock genes
• sudden sensorineural hearing loss

Disclosure statement

The authors of this study have no conflicts of interest.

Additional information

Funding

This work was supported by a Korean Medical Device Development Fund grant funded by the Korea Government (No. KMDF_PR_20210527_0007_2021_02).