Noise-induced hearing loss in zebrafish model: Characterization of tonotopy and sex-based differences.

Hearing loss caused by frequent and persistent exposure to loud noise is one of the most common diseases in modern society. Many studies have demonstrated the characteristics of noise-induced hearing loss in human and non-human vertebrate models, including frequency-specific noise-induced hearing loss and sex-biased differences. Zebrafish (Danio rerio) is a useful hearing research model because its lateral line is easy to access and because of its detailed perception of sound. Despite the increasing popularity of zebrafish as a model for NIHL, a better understanding of this model is needed to determine sex differences in NIHL. To study the features of zebrafish as they relate to an NIHL model, we tested various phenotypes after frequency-specific noise stimulation. The degree of damage to hair cells and hearing loss were investigated after exposing zebrafish to 200 Hz and 1 kHz continuous waves and broadband white noise with a bandwidth from 50 Hz to 1 kHz. After exposure to all frequencies, the larvae showed lateral line hair cell damage, which is superficially located. In adult zebrafish, the threshold of auditory-evoked potential signals is elevated. Moreover, the number of hair cells remarkably decreased in the rostral region of the saccule, after exposure to 1 kHz and white noise, whereas zebrafish exposed to 200 Hz noise showed a decrease in hair cells in the caudal region. Moreover, male zebrafish were found to be more vulnerable to noise than female zebrafish, as is the case in humans and other mammals. Cortisol levels also increased in the noise-exposed male group, as compared to the noise-exposed female and control male groups. However, there was no difference in cortisol levels when the noise-exposed female group was compared to the control female group. Our study demonstrates not only that noise-induced hearing loss is frequency-dependent but also that the degree of hearing loss is affected by sex in zebrafish, emphasizing the need to consider sex in NIHL studies.