Abstract

Age-related hearing loss (ARHL) is the progressive, bilateral loss of high-frequency hearing in elderly people. Mutations in GJB2, encoding the cochlear gap junction protein connexin26 (Cx26), are the most frequent cause of hereditary deafness; however, a common molecular pathology between ARHL and GJB2-related hearing loss has not been reported. Here, we investigated the quantitative change in expression and molecular pathology of Cx26 in ARHL. We used C57BL/6J mice as a model of ARHL. Hearing levels that were evaluated by auditory brainstem response thresholds increased gradually between 4 and 32 weeks of age and increased sharply at 36 weeks. Gap junctions in the cochleae of 4-week-old mice had linear plaques along cell–cell junction sites. In contrast, the cochleae from 32-week-old mice had significantly shorter gap junctions. Severe hair cell loss was not observed during this period. Based on western blotting, Cx26 and connexin30 (Cx30) levels were significantly decreased at 32 weeks compared with 4 weeks.Moreover, Cx26 was more significantly enriched in the hydrophilic fraction at 4 weeks but was more significantly enriched in the hydrophobic fraction at 32 weeks, indicating an age-related conversion of this biochemical property. Thus, the hydrophobic conversion of Cx26 and disruption of gap junction proteins and plaques may be involved in the pathogenesis of ARHL and may occur before severe hair cell degeneration.

Highlights

  • Age-related hearing loss (ARHL), known as presbycusis, is a growing problem because of the increase in the elderly population

  • Progression of hearing loss in aging C57BL/6J mice To assess changes in the hearing of C57BL/6J mice with age, auditory brainstem response (ABR) thresholds were recorded at 4 weeks of age and monitored regularly from 20 to 36 weeks of age (Fig. 1a)

  • Changes in gap junction plaques (GJPs) during early ARHL To assess the mechanisms of hearing loss at an earlier stage, we performed a detailed analysis of cochlear GJPs of the inner sulcus cells (ISCs) in 4- and 32-week-old mice

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Summary

Introduction

Age-related hearing loss (ARHL), known as presbycusis, is a growing problem because of the increase in the elderly population. Hearing loss of all types affects communication and quality of life. Recent evidence suggests that hearing loss may be an early sign of and contributor to dementia[1]. The use of hearing aids is recommended as a treatment for ARHL, but there are currently no treatments that can restore hearing. The mechanisms of aging in the auditory system have been the subject of investigation for decades. It has been proposed that ARHL can be explained largely by the degeneration of the lateral wall of the cochlea, which includes the stria vascularis, minor losses of the outer and inner hair cells (OHCs and IHCs, respectively), and some loss of spiral ganglion cells[2].

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