Halonen Joshua, Hinton Ashley S, Frisina Robert D, Ding Bo, Zhu Xiaoxia, Walton Joseph P
Departments of Communication Sciences and Disorders, University of South Florida, Tampa, FL 33620, USA; Global Center of Speech and Hearing Research, University of South Florida, Tampa, FL 33620, USA.
Departments of Communication Sciences and Disorders, University of South Florida, Tampa, FL 33620, USA; Chemical and Biomedical Engineering, University of South Florida, Tampa, FL 33620, USA; Global Center of Speech and Hearing Research, University of South Florida, Tampa, FL 33620, USA.
Hear Res. 2016 Jun;336:63-71. doi: 10.1016/j.heares.2016.05.001. Epub 2016 May 5.
Age-related hearing loss (ARHL), clinically referred to as presbycusis, is one of the three most prevalent chronic medical conditions of our elderly, with the majority of persons over the age of 60 suffering from some degree of ARHL. The progressive loss of auditory sensitivity and perceptual capability results in significant declines in workplace productivity, quality of life, cognition and abilities to communicate effectively. Aldosterone is a mineralocorticoid hormone produced in the adrenal glands and plays a role in the maintenance of key ion pumps, including the Na-K(+)-Cl co-transporter 1 or NKCC1, which is involved in homeostatic maintenance of the endocochlear potential. Previously we reported that aldosterone (1 μM) increases NKCC1 protein expression in vitro and that this up-regulation of NKCC1 was not dose-dependent (dosing range from 1 nM to 100 μM). In the current study we measured behavioral and electrophysiological hearing function in middle-aged mice following long-term systemic treatment with aldosterone. We also confirmed that blood pressure remained stable during treatment and that NKCC1 protein expression was upregulated. Pre-pulse inhibition of the acoustic startle response was used as a functional measure of hearing, and the auditory brainstem response was used as an objective measure of peripheral sensitivity. Long-term treatment with aldosterone improved both behavioral and physiological measures of hearing (ABR thresholds). These results are the first to demonstrate a protective effect of aldosterone on age-related hearing loss and pave the way for translational drug development, using aldosterone as a key component to prevent or slow down the progression of ARHL.
年龄相关性听力损失（ARHL），临床上称为老年性聋，是老年人中三种最常见的慢性疾病之一，60岁以上的大多数人都患有某种程度的ARHL。听觉敏感性和感知能力的逐渐丧失导致工作场所生产力、生活质量、认知能力和有效沟通能力显著下降。醛固酮是一种在肾上腺产生的盐皮质激素，在维持关键离子泵中起作用，包括钠-钾（+）-氯共转运体1或NKCC1，它参与内淋巴电位的稳态维持。此前我们报道，醛固酮（1μM）在体外可增加NKCC1蛋白表达，且这种NKCC1的上调不依赖剂量（剂量范围为1 nM至100μM）。在本研究中，我们测量了中年小鼠长期全身用醛固酮治疗后的行为和电生理听力功能。我们还证实治疗期间血压保持稳定，且NKCC1蛋白表达上调。声惊吓反应的预脉冲抑制用作听力的功能指标，听觉脑干反应用作外周敏感性的客观指标。长期用醛固酮治疗可改善听力的行为和生理指标（ABR阈值）。这些结果首次证明了醛固酮对年龄相关性听力损失具有保护作用，并为转化药物开发铺平了道路，将醛固酮作为预防或减缓ARHL进展的关键成分。
