Li Pengjun, Bing Dan, Wang Sumei, Chen Jin, Du Zhihui, Sun Yanbo, Qi Fan, Zhang Yingmiao, Chu Hanqi
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Neurosci. 2019 Nov 29;13:1297. doi: 10.3389/fnins.2019.01297. eCollection 2019.
A lack of sleep is linked with a range of inner ear diseases, including hearing loss and tinnitus. Here, we used a mouse model to investigate the effects of sleep deprivation (SD) on noise vulnerability, and explored the mechanisms that might be involved , focusing particularly corticosterone levels and autophagic flux in cells. Female BALB/c mice were divided into six groups [control, acoustic trauma (AT)-alone, 1 day (d) SD-alone, 1d SD pre-AT, 5d SD-alone, and 5d SD pre-AT]. Cochlear damage was then assessed by analyzing auditory brainstem response (ABR), and by counting outer hair cells (OHCs) and the synaptic ribbons of inner hair cells (IHCs). In addition, we measured levels of serum corticosterone and autophagy protein expression in the basilar membranes by ELISA kits, and western blotting, respectively. We found that SD-alone temporarily elevated ABR wave I amplitude, but had no permanent effect on hearing level or IHC ribbon numbers. Combined with AT, the number of synaptic ribbons in the 1d SD pre-AT group was significantly higher than that in the AT-alone group, whereas the 5d SD pre-AT group showed more severe synaptopathy, and a greater loss of OHCs after 2 weeks than the other experimental groups exposed to noise. Correspondingly, the levels of corticosterone in the AT-alone group were higher than those of the 1d SD pre-AT group, but lower than those of the 5d SD pre-AT group. The 1d SD pre-AT group showed a marked elevation in the expression of microtubule-associated protein 1 light chain 3B (LC3B), whereas the AT-alone group exhibited only a mild increase. In contrast, the levels of LC3B did not change in the 5d SD pre-AT group. Experiments with HEI-OC-1 cells and cochlear basilar membrane cultures showed that high-concentrations of dexamethasone, and the inhibition of autophagy, aggravated cellular apoptosis induced by oxidative stress. In conclusion, noise-induced synaptopathy and hair cell loss can be mitigated by preceding 1d SD, but will be aggravated by preceding 5d SD. These findings may be attributable to corticosterone levels and the extent of autophagy.
睡眠不足与一系列内耳疾病有关，包括听力损失和耳鸣。在此，我们使用小鼠模型来研究睡眠剥夺（SD）对噪声易感性的影响，并探索可能涉及的机制，特别关注细胞中的皮质酮水平和自噬通量。将雌性BALB/c小鼠分为六组[对照组、单独声创伤（AT）组、单独1天（d）SD组、AT前1天SD组、单独5天SD组和AT前5天SD组]。然后通过分析听性脑干反应（ABR）以及计数外毛细胞（OHC）和内毛细胞（IHC）的突触带，评估耳蜗损伤情况。此外，我们分别通过ELISA试剂盒和蛋白质免疫印迹法测量血清皮质酮水平以及基底膜中自噬蛋白的表达。我们发现，单独的SD会暂时提高ABR波I的振幅，但对听力水平或IHC突触带数量没有永久性影响。与AT联合时，AT前1天SD组的突触带数量显著高于单独AT组，而AT前5天SD组在2周后显示出更严重的突触病变以及比其他噪声暴露实验组更严重的OHC损失。相应地，单独AT组的皮质酮水平高于AT前1天SD组，但低于AT前5天SD组。AT前1天SD组微管相关蛋白1轻链3B（LC3B）的表达显著升高，而单独AT组仅略有增加。相比之下，AT前5天SD组的LC3B水平没有变化。对HEI-OC-1细胞和耳蜗基底膜培养物进行的实验表明，高浓度地塞米松以及自噬抑制会加重氧化应激诱导的细胞凋亡。总之，噪声诱导的突触病变和毛细胞损失可通过提前1天SD得到缓解，但会因提前5天SD而加重。这些发现可能归因于皮质酮水平和自噬程度。
