Association between Cav3 channel upregulation in spiral ganglion neurons and age-dependent hearing loss.

Cav3 channels play a critical role in maintaining calcium homeostasis, and its dysregulation is related to age-related diseases, such as age-related hearing loss (AHL). However, the underlying mechanism of the Cav3 channels involved in AHL remains unknown. Previous studies have shown that the degeneration of spiral ganglion neurons (SGNs) plays a critical role in AHL. Here, we explored the involvement of Cav3 channels in the dysregulation of SGNs in AHL. We used C57BL/6 mice as the AHL mouse model and found that the expression of Cav3 channels was increased in SGNs associated with age. The three subtypes of Cav3 channels were present in the apical, middle, and basal SGNs from young and older (AHL) mice. The immunostaining data suggest that Cav3.1 and Cav3.2 may contribute to Cav3 upregulation in SGNs of AHL mice. Additionally, we found that calpain-2 and apoptosis-inducing factor (AIF) were activated in SGNs from AHL mice. The inhibition of Cav3 channels or calpain-2 reduced AIF-activation in SGNs may affect neuronal survival. In conclusion, the findings suggest that Cav3 channels are upregulated in SGNs from AHL mice that may contribute to the degeneration of SGNs through the calpain-2-AIF apoptosis pathway in AHL mice.