Pineros Jennifer, Zhu Xiaoxia, Ding Bo, Frisina Robert D
Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL 33620, USA; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA.
Department of Medical Engineering, College of Engineering, University of South Florida, Tampa, FL 33620, USA; Global Center for Hearing and Speech Research, University of South Florida, Tampa, FL 33612, USA; Department of Communication Sciences and Disorders, College of Behavioral & Community Sciences, University of South Florida, Tampa, FL 33620, USA; Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA.
Hear Res. 2024 Mar 15;444:108971. doi: 10.1016/j.heares.2024.108971. Epub 2024 Feb 11.
Age-related hearing loss (ARHL), also known as presbycusis, is the number one communication disorder for aging adults. Connexin proteins are essential for intercellular communication throughout the human body, including the cochlea. Mutations in connexin genes have been linked to human syndromic and nonsyndromic deafness; thus, we hypothesize that changes in connexin gene and protein expression with age are involved in the etiology of ARHL. Here, connexin gene and protein expression changes for CBA/CaJ mice at different ages were examined, and correlations were analyzed between the changes in expression levels and functional hearing measures, such as ABRs and DPOAEs. Moreover, we investigated potential treatment options for ARHL. Results showed significant downregulation of Cx30 and Cx43 gene expression and significant correlations between the degree of hearing loss and the changes in gene expression for both genes. Moreover, dose-dependent treatments utilizing cochlear cell lines showed that aldosterone hormone therapy significantly increased Cx expression. In vivo mouse treatments with aldosterone also showed protective effects on connexin expression in aging mice. Based on these functionally relevant findings, next steps can include more investigations of the mechanisms related to connexin family gap junction protein expression changes during ARHL; and expand knowledge of clinically-relevant treatment options by knowing what specific members of the Cx family and related inter-cellular proteins should be targeted therapeutically.
年龄相关性听力损失（ARHL），也称为老年性聋，是老年人首要的交流障碍。连接蛋白对于包括耳蜗在内的整个人体的细胞间通讯至关重要。连接蛋白基因突变与人类综合征性和非综合征性耳聋有关；因此，我们推测连接蛋白基因和蛋白表达随年龄的变化与ARHL的病因有关。在此，研究了不同年龄CBA/CaJ小鼠连接蛋白基因和蛋白表达的变化，并分析了表达水平变化与功能性听力指标（如听性脑干反应（ABR）和畸变产物耳声发射（DPOAE））之间的相关性。此外，我们还研究了ARHL的潜在治疗方案。结果显示Cx30和Cx43基因表达显著下调，且听力损失程度与这两个基因的表达变化之间存在显著相关性。此外，利用耳蜗细胞系进行的剂量依赖性治疗表明，醛固酮激素疗法可显著增加连接蛋白的表达。对小鼠进行醛固酮体内治疗也显示出对衰老小鼠连接蛋白表达的保护作用。基于这些功能相关的发现，接下来的步骤可以包括更多地研究ARHL期间连接蛋白家族间隙连接蛋白表达变化的相关机制；通过了解应作为治疗靶点的Cx家族的特定成员和相关细胞间蛋白，扩展对临床相关治疗方案的认识。
