Up-regulation of autophagy and apoptosis of cochlear hair cells in mouse models for deafness

Abstract

Introduction: Hearing loss is one of the most common sensory disorders. Recent findings have shown that the apoptotic program and autophagy are related to hearing loss. The aim of the study was to explore the effects of noise and cisplatin exposure on apoptosis and autophagy in the hair cells of the cochleae. Material and methods: C57BL/6 mice were randomly divided into 3 groups (n = 10 for each): The control group, the noise model group and the cisplatin model group. Auditory brainstem response (ABR) measurements were used to detect the hearing thresholds. TUNEL assay was used to evaluate cell apoptosis. Western blot and immunofluorescence were performed to examine the apoptosis- and autophagy-related proteins. Results: The mice exhibited substantial hearing loss after noise and cisplatin exposure. Additionally, more TUNEL positive cells were observed in the mice after noise and cisplatin exposure compared with the control group. Moreover, the protein expression levels of Beclin-1, LC3-II, Bax and cleaved caspase-3 were significantly increased, while the expression of Bcl-2 was notably decreased in the cochlea after noise (p = 0.0278, 0.0075, 0.0142, 0.0158, 0.0131 respectively) and cisplatin (p = 0.0220, 0.0075, 0.0024, 0.0161, 0.0452 respectively) exposure compared with the control group. Besides, the ratio of LC3-II/LC3-I was substantially higher in the mice treated by cisplatin (p = 0.0046) and noise (p = 0.0220) compared with the control group. Conclusions: Our findings demonstrated for the first time that noise and cisplatin exposure promoted apoptosis and autophagy in the hair cells of the cochleae. This study provides new insights into the mechanisms of noise- or cisplatin-induced hearing loss.