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目的 基于一种基因敲入小鼠(C57BL/6-Atp6v1b2Arg506X/Arg506X)的隐性听力损失(Hidden hearing loss,HHL表型探索HHL小鼠噪声暴露后听力损失发生、发展机制。方法 12周隐性听力损失模型小鼠各6只，野生型、纯合型同窝对照，给予白噪声75dB SPL暴露8小时，于噪声前、噪声暴露后1天、7天、14天行听性脑干反应(Auditory brainstem response,ABR)测试分析两组小鼠听力学差异，取2组小鼠耳蜗组织，免疫荧光染色观察内外毛细胞及内毛细胞带状突触数量变化，分析毛细胞内自噬蛋白表达。结果 低强度噪声暴露后，纯合组小鼠较野生型小鼠听力下降明显，纯合小鼠带状突触计数较野生型减少，纯合小鼠毛细胞自噬蛋白表达量较野生型降低，且内外毛细胞无明显损失。结论 HHL可能具有遗传基础且对噪声具有易感性。HHL小鼠噪声暴露后听力下降与溶酶体功能进一步降低、带状突触数量减少相关。全面的听力检测及基因检测有助于早期诊断隐匿性耳聋。噪声防护在隐性听力损失个体尤为重要。
Abstract：Objective To understand genetic susceptibility to hearing loss in a mouse model of hidden hearing loss(HHL)(C57BL/6-Atp6v1b2Arg506X/Arg506X) exposed to low intensity noise. Methods Six 12-week-old Atp6v1b2 c.1516C>T knock-in mice(the HHL group) and four wild-type homozygous littermates(controls) were exposed to white noise at 75 dB SPL for 8 hours, and tested for auditory brainstem responses(ABR) before, and 1, 7 and 14 days after noise exposure. Fourteen days after the noise exposure, cochlear tissues were collected to determine changes in the number of inner and outer hair cells and ribbon synapses by immunofluorescence staining, and in expression of autophagy proteins in hair cells. Results Following noise exposure, more hearing loss was noticed in Atp6v1b2 c.1516 C>T knock-in mice than in wild-type mice, with greater number of lost ribbon synapses and lower levels of autophagy protein expression in hair cells. There was no significant loss of inner or outer hair cells. Conclusions Mice with HHL may be genetically predisposed to noise-induced damage. Comprehensive hearing and genetic testing can help in early diagnosis of HHL.Noise protection is especially important in individuals with HHL.
1 Liberman MC. Hidden hearing loss[J]. Sci Am, 2015;313(2):48-53.
2 Qiu S,Zhao W,Gao X,et al.Syndromic deafnessgene ATP6V1B2controls degeneration of spiral ganglion neurons through modulating proton flux[J]. Front Cell Dev Biol, 2021;9:742714.
3 Yuan Y, Zhang J, Chang Q, et al. De novo mutation in ATP6V1B2impairs lysosome acidification and causes dominant deafness-onychodystrophy syndrome[J]. Cell Res, 2014;24(11):1370-1373.
4 Zhao W, Gao X, Qiu S, et al. A subunit of V-ATPases, ATP6V1B2,underlies the pathology of intellectual disability[J]. E Bio Medicine, 2019;45:408-421.
5 C Kohrman D, Wan G, Cassinotti L, et al. Hidden hearing loss:a disorder with multiple etiologies and mechanisms[J]. Cold Spring Harb Perspect Med, 2020;10(1):a035493.
6 Kujawa SG, Liberman MC. Adding insult to injury:cochlear nerve degeneration after"temporary"noise-induced hearing loss[J]. J Neurosci, 2009;29(45):14077-14085.
7 Shi L, Liu K, Wang H, et al. Noise induced reversible changes of cochlear ribbon synapses contribute to temporary hearing loss in mice[J]. Acta Otolaryngol, 2015;135(11):1093-1102.
8 Muniak MA, Ayeni FE, Ryugo DK. Hidden hearing loss and endbulbs of held:evidence for central pathology before detection of ABR threshold increases[J]. Hear Res, 2018;364:104-117.
9 Hong J, Chen Y, Zhang Y, et al. N-Methyl-D-Aspartate receptors involvement in the gentamicin-induced hearing loss and pathological changes of ribbon synapse in the mouse cochlear inner hair cells[J]. Neural Plast, 2018;2018:3989201.
10 Choi JE, Seok JM, Ahn J, et al. Hidden hearing loss in patients with Charcot-Marie-Tooth disease type 1A. Sci Rep, 2018; 8(1):10335.
11 Zhou R, Assouline JG, Abbas PJ, et al. Anatomical and physiological measures of auditory system in mice with peripheral myelin deficiency. Hear Res, 1995; 88(1-2):87-97.
12 Fernandez KA, Guo D, Micucci S, et al. Noise-induced cochlear synaptopathy with and without sensory cell loss[J]. Neuroscience, 2020;427:43-57.
13 Wang Y, Hirose K, Liberman MC. Dynamics of noise-induced cellular injury and repair in the mouse cochlea[J]. J Assoc Res Otolaryngol, 2002;3(3):248-268.
14 Schaette R, McAlpine D. Tinnitus with a normal audiogram:physiological evidence for hidden hearing loss and computational model[J]. J Neurosci, 2011;31(38):13452-13457.
15 Lobarinas E, Spankovich C, Le Prell CG. Evidence of"hidden hearing loss"following noise exposures that produce robust TTS and ABR wave-I amplitude reductions[J]. Hear Res, 2017; 349:155-163.
16 Abbas YM, Wu D, Bueler SA, et al. Structure of V-ATPase from the mammalian brain[J]. Science, 2020;367(6483):1240-1246.
17 Vernon PJ, Tang D. Eat-me:autophagy, phagocytosis, and reactive oxygen species signaling[J]. Antioxid Redox Signal, 2013;18(6):677-691.
18 Yuan H, Wang X, Hill K, et al. Autophagy attenuates noise-induced hearing loss by reducing oxidative stress[J]. Antioxid Redox Signal, 2015;22(15):1308-1324.
19 赵伟豪，袁永一，韩维举.溶酶体异常与耳聋[J].中华耳科学杂志，2017,15(2):249-256.ZHAO Weihao, YUAN Yongyi, HAN Weiju. Lysosomal impairment and deafness[J] Chinese Journal of Otology, 2017, 15(2):249-256.
基本信息:
中图分类号:R764.43;R-332
引用信息:
[1]赵超越,杨金源,王伟倩,等.隐性听力损失小鼠模型的噪声性聋易感性研究[J].中华耳科学杂志,2023,21(03):367-371.
基金信息:
军委科技委基础加强计划重点项目（2020-JCJQ ZD-262-00）; 国家自然科学基金面上项目（82271177,82271185）~~
2023-06-15
2023-06-15