The role of GDF15 in attenuating noise-induced hidden hearing loss by alleviating oxidative stress

Abstract

Noise-induced hidden hearing loss (HHL) is a newly uncovered form of hearing impairment that causes hidden damage to the cochlea. Patients with HHL do not have significant abnormalities in their hearing thresholds, but they experience impaired speech recognition in noisy environments. However, the mechanisms underlying HHL remain unclear. In this study, we developed single-cell transcriptome profiles of the cochlea of mice with HHL, detailing changes in individual cell types. Our study revealed a transient threshold shift, reduced auditory brainstem response wave I amplitude, and decreased number of ribbon synapses in HHL mice. Our findings suggest elevated oxidative stress and GDF15 expression in cochlear hair cells of HHL mice. Notably, the upregulation of GDF15 attenuated oxidative stress and auditory impairment in the cochlea of HHL mice. This suggests that a therapeutic strategy targeting GDF15 may be efficacious against HHL.

Graphical Abstract

1. HHL mice had a transient threshold shift, reduced ABR wave I amplitude, and decreased number of ribbon synapses.

2. HHL mice's cochlear hair cells exhibited increased oxidative stress and elevated GDF15 expression.

3. Upregulation of GDF15 attenuated oxidative stress and auditory damage in the cochlea of HHL mice, implying that GDF15-targeted treatment techniques may be useful for HHL.

Supplementary Information

The online version contains supplementary material available at 10.1007/s10565-024-09912-2.