Ruan Q, Zeng S, Liu A, Chen Z, Yu Z, Zhang R, He J, Bance M, Robertson G, Yin S, Wang J
1] Department and Research Institute of Otolaryngology, The Sixth Affiliated Hospital of Shanghai Jiaotong University, Shanghai, People's Republic of China [2] Research Center of Aging and Medicine, Shanghai Key Laboratory of Clinical Geriatrics, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Department and Research Institute of Otolaryngology, The Sixth Affiliated Hospital of Shanghai Jiaotong University, Shanghai, People's Republic of China.
Gene Ther. 2014 Nov;21(11):967-74. doi: 10.1038/gt.2014.77. Epub 2014 Aug 21.
Previously, we showed that age-related hearing loss (AHL) was delayed in C57BL6 mice overexpressing X-Linked Inhibitor of Apoptotic Protein (XIAP), and the delayed AHL was associated with attenuated hair cell (HC) loss in XIAP-overexpressing mice. Similar to other reports, the HC loss in aged mice was restricted to the basal turn in this previous study, and occurred slightly at the apical end of the cochlea, showing considerably less spread than the frequency region of hearing loss. In the present study, we examined whether and how AHL is related to the degeneration of neuronal innervation of the cochlea and whether the overexpression of XIAP exerts a protective effect against age-related degeneration in both afferent and efferent cochlear neurites. In contrast to HC loss, degeneration of both afferent and efferent neurites spread to the middle turns of the cochlea. Moreover, XIAP-overexpressing mice lost fewer HC afferent dendrites and efferent axons, as well as fewer spiral ganglion neurons between 3 and 14 months of age in comparison with wild-type littermates. The results suggest that age-related degeneration of cochlear neurites may be independent of HC loss. Further, the inhibition of apoptosis by XIAP appears to reduce degeneration of both afferent and efferent cochlear neurites.
先前，我们发现过表达X连锁凋亡抑制蛋白（XIAP）的C57BL6小鼠的年龄相关性听力损失（AHL）出现延迟，且这种延迟的AHL与XIAP过表达小鼠中毛细胞（HC）损失的减轻有关。与其他报道相似，在之前的这项研究中，老年小鼠的HC损失局限于蜗底，在耳蜗顶端略有发生，其扩散程度远小于听力损失的频率区域。在本研究中，我们研究了AHL是否以及如何与耳蜗神经支配的退化相关，以及XIAP的过表达是否对传入和传出耳蜗神经纤维的年龄相关性退化具有保护作用。与HC损失不同，传入和传出神经纤维的退化都蔓延至耳蜗的中回。此外，与野生型同窝小鼠相比，XIAP过表达小鼠在3至14月龄时损失的HC传入树突、传出轴突以及螺旋神经节神经元数量更少。结果表明，耳蜗神经纤维的年龄相关性退化可能独立于HC损失。此外，XIAP对细胞凋亡的抑制作用似乎减少了传入和传出耳蜗神经纤维的退化。
