D-galactose administration via semicircular canal induces accelerated cochlear aging: A novel model of oxidative stress-mediated presbycusis.

Chunli Zhao, Zijing Yang, Zhongrui Chen, Ke Liu, Zhengde Du, Shusheng Gong

Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; Clinical Center for Hearing Loss, Capital Medical University, Beijing 100050, China.Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; Clinical Center for Hearing Loss, Capital Medical University, Beijing 100050, China. · pubmed

Paper

Abstract

Age-related hearing loss (ARHL) is a progressive, bilateral sensorineural impairment with significant socio-psychological consequences. Current ARHL models (natural aging or systemic D-galactose (D-gal) injection) face limitations: prolonged timelines, high variability, and inconsistent D-gal protocols. To concentrate aging pathology within the peripheral auditory system, we developed a novel accelerated cochlear aging model by targeted delivery of D-gal via the posterior semicircular canal. This approach aimed to concentrate aging pathology within the peripheral auditory system. Auditory brainstem response testing was employed to assess murine hearing thresholds for determining optimal D-gal concentration and exposure duration. Results demonstrated that by post-administration day 14, the D-gal-H group exhibited pronounced auditory characteristics consistent with ARHL. Morphological staining further revealed significant outer hair cells loss and ribbon synapses degeneration. Concurrently, immunohistochemical analysis of 4-HNE and 8-OHdG showed elevated oxidative stress levels in the stria vascularis, spiral ganglion cells, and inner hair cells of D-gal-treated groups. Substantial alterations in aging-associated proteins were also observed. Mitochondrial membrane potential assessment indicated significant depolarization in treated cochleae. Accordingly, we established a rapid, targeted, and pathologically validated model of cochlear aging, which provides a valuable tool for investigating the mechanisms underlying peripheral auditory aging.

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Research summary

The paper claims to establish a novel accelerated cochlear aging model through targeted D-galactose administration. This research is relevant as it addresses mechanisms of aging within the auditory system, contributing to the understanding of age-related hearing loss and potentially offering insights into broader aging processes.

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