螺旋神经节
耳蜗
细胞凋亡
毛细胞
内耳
半胱氨酸蛋白酶
听力损失
半胱氨酸蛋白酶3
科尔蒂器官
内分泌学
男科
生物
内科学
医学
程序性细胞死亡
解剖
听力学
遗传学
作者
Linlin Yang,Heng Zhang,Han Xu,Xin Zhao,Fangyuan Hu,Ping Li,Gang Xie,Lixiang Gao,Lin Cheng,Xicheng Song,Fengchan Han
标识
DOI:10.1016/j.heares.2015.05.006
摘要
DBA/2J mice are characterized by early onset hearing loss at about 3-4 weeks of age. Mutations in cadherin 23 (Cdh23) and fascin-2 (Fscn2) are responsible for the phenotypes, but the underlying mechanism is unknown. In the present study, DBA/2J mice displayed progressive hair cell loss and degeneration of spiral ganglion neurons (SGNs) after 2 weeks of age; however, the mRNA level of Caspase-3 in the inner ears was much higher at 2 weeks of age than that at 4 or 8 weeks of age. Moreover, transcriptional levels of Caspase-3 and Caspase-9 in the inner ears of DBA/2J mice were significantly higher than those of C57BL/6J mice at 2 or 8 weeks of age. Immunohistochemistry localized Caspase-3 and Caspase-9 mainly to the hair cells, SGNs and stria vascularis of the cochleae. To determine the significance of caspase-dependent apoptosis in the hearing loss, the pan-caspase inhibitor Z-VAD-FMK was given intraperitoneally to DBA/J2 mice over an 8-week period starting at one week of age. Blockage of caspases preserved hearing in the mice by more than 10 dB (dB) sound pressure level (SPL) of the ABR thresholds and significantly reduced outer hair cell loss at the basal turns of the cochleae. These results demonstrate that apoptosis in the cochleae of DBA/J2 mice contributes to the early onset of hearing loss, which can be attenuated by anti-apoptotic treatment.
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