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

The cochlea contains a robust biological clock associated with auditory function, exhibiting diurnal sensitivity to noise or ototoxicity 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. 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 <i>PERI</i>, <i>PER2</i>, <i>PER3</i>, <i>CRYI</i>, <i>CRY2</i>, <i>CLOCK</i>, <i>ARNTL</i>, <i>CSNKIE</i>, and <i>TIMELESS</i> expression in blood were evaluated using real-time quantitative PCR method. 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. This study provides an additional basis for the relevance of disrupted circadian rhythm to SSNHL and suggests a possible prognostic biomarker for SSNHL treatment.

耳蜗存在与听觉功能紧密关联的稳定生物钟，其对噪声或耳毒性物质呈现昼夜节律性敏感特性。本研究在突发性感音神经性耳聋（sudden sensorineural hearing loss, SSNHL）患者群体中，探究了节律紊乱与生物钟基因表达异常之间的关联，并探讨了生物钟基因是否可作为预后生物标志物。本研究纳入12例SSNHL患者作为研究组，同时招募12名听力正常者自愿参与对照。通过听力学评估检测受试者的听力阈值，采用韩国版匹兹堡睡眠质量指数问卷（Pittsburgh Sleep Quality Index Questionnaire）评估受试者的睡眠质量与睡眠模式，并通过实时定量聚合酶链反应（real-time quantitative PCR）检测外周血中PERI、PER2、PER3、CRYI、CRY2、CLOCK、ARNTL、CSNKIE及TIMELESS等生物钟基因的表达水平。结果显示，与听力正常的健康对照者相比，SSNHL患者体内多数生物钟基因的表达显著下调，同时伴随睡眠质量低下与睡眠模式紊乱。值得注意的是，类固醇治疗后的听力改善程度与生物钟基因表达水平的变化之间存在微弱相关性。本研究为节律紊乱与SSNHL的相关性提供了新的佐证，并提示生物钟基因可作为SSNHL治疗潜在的预后生物标志物。