Constant Light Dysregulates Cochlear Circadian Clock and Exacerbates Noise-Induced Hearing Loss.

Chao-Hui Yang,Wei-Shiung Lian,Jiin-Haur Chuang,Ethan I Huang,Ming-Yu Yang,Chung-Feng Hwang,Feng-Sheng Wang

doi:10.3390/ijms21207535

Abstract

Noise-induced hearing loss is one of the major causes of acquired sensorineural hearing loss in modern society. While people with excessive exposure to noise are frequently the population with a lifestyle of irregular circadian rhythms, the effects of circadian dysregulation on the auditory system are still little known. Here, we disturbed the circadian clock in the cochlea of male CBA/CaJ mice by constant light (LL) or constant dark. LL significantly repressed circadian rhythmicity of circadian clock genes Per1, Per2, Rev-erbα, Bmal1, and Clock in the cochlea, whereas the auditory brainstem response thresholds were unaffected. After exposure to low-intensity (92 dB) noise, mice under LL condition initially showed similar temporary threshold shifts to mice under normal light–dark cycle, and mice under both conditions returned to normal thresholds after 3 weeks. However, LL augmented high-intensity (106 dB) noise-induced permanent threshold shifts, particularly at 32 kHz. The loss of outer hair cells (OHCs) and the reduction of synaptic ribbons were also higher in mice under LL after noise exposure. Additionally, LL enhanced high-intensity noise-induced 4-hydroxynonenal in the OHCs. Our findings convey new insight into the deleterious effect of an irregular biological clock on the auditory system.

Highlights

The circadian clock and rhythm are important for the regulation of tissue homeostasis and function
The localization of PER2 was mainly observed in the organ of Corti, with strong PER2 immunofluorescence at zeitgeber time 12 (ZT12) and weak immunoreaction at ZT4 (Supplementary Figure S1)
In agreement with the groundbreaking studies of Canlon and colleagues [9], we demonstrated the oscillated expression of circadian clock genes in the cochlea of CBA/CaJ mice

Summary

Introduction

The circadian clock and rhythm are important for the regulation of tissue homeostasis and function. The severity of kanamycin-mediated ototoxicity is correlated with diurnal sensitivity of rats [8]. Park et al demonstrated a circadian clock in the cochlea and inferior colliculus of adult mice [10] as well as a differential phase arrangement of cellular clocks along the tonotopic axis (base to apex) of mouse cochlear explants [11]. These findings imply a possible role of circadian regulation in auditory function [12,13]

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