Purpose: This study was carried out to investigate incidence of autophagy and apoptosis in spiral ganglion cells (SGCs) and cochlear nucleus neurons, and their involvement in the pathogenesis of diabetes-induced hearing impairment in rats.
Methods: Rats were randomly divided into control group and diabetes groups, with variations in duration of diabetes: 4 weeks (DM4W), 8 weeks (DM8W) and 12 weeks (DM12W). Diabetes was induced by intraperitoneal injection of streptozotocin. The rats of each group were tested with auditory brainstem response (ABR). Ultra-structures of cochlear nuclei and SGCs were examined by transmission electron microscope. Western blot and immunehistochemical methods were used to for estimating the expression of autophagy-related factors (Beclin 1 and cleaved-LC3); apoptosis-related factors (Bax, Bcl-2 and cleaved Caspase-3 protein) in cochlear nuclei and SGCs.
Results: ABR response thresholds of rats in DM8W and DM12W group were increased significantly. Compared to control group, the latency and wave duration of DM12W group were higher. Mitochondria swelling and vacuoles were observed in SGCs of diabetes group. More lysosomes and myelin layer plate fractures were seen in cochlear nuclei of diabetes group. The expression of Beclin 1, cleaved-LC3, Bax and cleaved Caspase-3 protein in DM8W and DM12W groups increased, while expression of Bcl-2 was decreased, both significantly.
Conclusion: The results show that autophagy and apoptosis are implicated in the development of hearing impairment in diabetic ratss.