Hearing Research最新文献_第2页

Vestibular habituation is associated with distinct autonomic signatures and greater reduction in visually induced motion sickness: A randomized controlled trial 前庭习惯化与明显的自主神经特征和视觉引起的晕动病的更大减少有关：一项随机对照试验。

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-01-30 DOI: 10.1016/j.heares.2026.109554

Qikun Zhang , Xinyang Chen , Chuanxia Cao , Yaqi Zhang , Jing Zhao , Linyao Shi , Shengguang Yan , Zhanguo Jin

This study compared the efficacy of short-duration, high-intensity versus stepwise, progressively lengthened optokinetic drum-chair training in alleviating visually induced motion sickness (VIMS) and modulating autonomic function. Ninety-six VIMS-susceptible university students were randomly assigned to either a short-duration (S-D) group (one training session daily for 3 consecutive days, with each session terminated upon the first report of pronounced nausea) or a stepwise (S-W) group underwent a 6-day graduated protocol (one session daily, duration: 60 s/120 s/180 s). Efficacy was assessed by comparing pre- and post-intervention 90-second chair-rotation challenges. The primary outcome was the Graybiel motion-sickness score (Graybiel score); secondary outcomes included frequency-domain heart rate variability (FD-HRV), electrodermal activity (EDA), and skin temperature (SKT). The S-W group showed a greater reduction in Graybiel scores than the S-D group (median change: -9.0 versus -5.0; between-group Hodges-Lehmann difference: -3.0 points; 95% CI -7.0 to -1.0). Autonomically, the S-W group reduced both low-frequency (LF) and high-frequency (HF) power and increased the LF/HF ratio, while The S-D group reduced only HF power. Skin conductance response amplitude (SCR) increased in the S-W group only. SKT decreased substantially (2-4 °C) in the S-D group but minimally (< 1 °C) in the S-W group (between-group P < 0.01, baseline-adjusted). In conclusion, the stepwise protocol was associated with greater VIMS symptom relief and a more favorable autonomic profile than the short-duration approach, suggesting it may serve as a potential non-pharmacological countermeasure for virtual reality or simulator settings.

本研究比较了短时间、高强度与逐步延长的光动力鼓椅训练在缓解视动病（VIMS）和调节自主神经功能方面的疗效。96名易患vims的大学生被随机分配到短时间（s -d）组（每天一次训练，连续3天，每次训练在第一次报告明显恶心时结束）或逐步（s - w）组，接受6天的逐步方案（每天一次，持续时间：60秒/120秒/180秒）。通过比较干预前和干预后90秒的椅子轮换挑战来评估疗效。主要结果为Graybiel晕车评分（Graybiel score）；次要结局包括频域心率变异性（FD-HRV）、皮电活动（EDA）和皮肤温度（SKT）。S-W组的Graybiel评分下降幅度大于S-D组（变化中位数：-9.0 vs -5.0；组间Hodges-Lehmann差值：-3.0分；95% CI: -7.0 ~ -1.0）。S-W组同时降低低频（LF）和高频（HF）功率，提高LF/HF比值，而S-D组仅降低高频功率。仅S-W组皮肤电导反应幅度（SCR）升高。S-D组SKT显著降低（2-4°C）， S-W组SKT最低（< 1°C）（经基线调整后，组间P < 0.01）。总之，与短时间方法相比，分步方案与更大的VIMS症状缓解和更有利的自主神经特征相关，这表明它可能作为虚拟现实或模拟器设置的潜在非药物对策。

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引用次数: 0

A porcine congenital deafness model with unconditional knockout of GJB2 generated by CRISPR/Cas9 genomic editing CRISPR/Cas9基因编辑构建无条件敲除GJB2的猪先天性耳聋模型

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-01-30 DOI: 10.1016/j.heares.2026.109552

Fei Xie (谢飞) , Xiaozhou Liu (刘晓宙) , Lulu Wang (王露露) , Cong Zhang (张聪) , Chuanhong Liu (刘传宏) , Zhenqing Huo (霍振庆) , Zhengdong Zhao (赵正东) , Qingyuan Zhao (赵清远) , Qiuyue He (贺秋月) , Kenan Guo (郭科男) , Yu Sun (孙宇) , Yong Wang (王勇)

GJB2, the primary gene responsible for DFNB1, the most prevalent non-syndromic hearing loss (NSHL), has variants that account for over 50% of all prelingual hearing loss (HL). Mice are the main model for congenital hearing loss (CHL) research, but they have delayed auditory maturation postnatally, and unconditional Gjb2 knockout in mice causes embryonic lethality. Pigs have similar inner-ear anatomy to humans and, like humans, have matured auditory function and fully differentiated cochlea at birth. Currently, there is no GJB2 unconditional knockout animal model for GJB2-related CHLs research, and whether unconditional GJB2 deletion causes embryonic lethality in pigs or if GJB2-deficient pigs can recapitulate typical clinical pathological characteristics remains unclear. In this study, we employed CRISPR/Cas9 to establish the first unconditional GJB2 knockout pig model. The mutant GJB2 alleles in the founder pig were stably germline-transmitted to subsequent generations. Homozygous GJB2 knockout pigs exhibited no embryonic lethality and showed profound hearing loss, cochlear hair cell depletion and impaired Organ of Corti’s development. This GJB2 unconditional knockout pig model has not been reported before and demonstrates GJB2 mutation pathological characteristics consistent with clinical patients, validating its potential in investigating the pathogenic mechanisms and therapeutic interventions of GJB2-deficient CHLs.

GJB2是最常见的非综合征性听力损失（NSHL） DFNB1的主要基因，其变异占所有语前听力损失（HL）的50%以上。小鼠是先天性听力损失（CHL）研究的主要模型，但小鼠出生后听觉成熟延迟，无条件敲除Gjb2会导致小鼠胚胎致死。猪的内耳解剖结构与人类相似，并且与人类一样，在出生时具有成熟的听觉功能和完全分化的耳蜗。目前还没有GJB2无条件敲除动物模型用于GJB2相关CHLs的研究，GJB2无条件敲除是否会导致猪的胚胎致死，或者GJB2缺陷猪是否能重现典型的临床病理特征，目前还不清楚。在本研究中，我们利用CRISPR/Cas9技术建立了首个无条件敲除GJB2的猪模型。始祖猪的突变体GJB2等位基因稳定地种系遗传给后代。GJB2纯合子敲除猪无胚胎致死性，表现为重度听力损失、耳蜗毛细胞缺失和Corti发育受损。该GJB2无条件敲除猪模型此前未见报道，其GJB2突变病理特征与临床患者一致，验证了其在研究GJB2缺陷CHLs的发病机制和治疗干预方面的潜力。

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引用次数: 0

Using vocoders to the implanted ear to investigate the binaural benefit for music sound quality in single-sided deaf cochlear implant users 应用声码器对单侧耳蜗植入者的双耳音乐音质进行研究。

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-01-29 DOI: 10.1016/j.heares.2026.109548

Sean Lang , John J. Galvin III , Isaac Cooley , Natalia Stupak , David M. Landsberger

Despite the poor sound quality provided by cochlear implants (CIs), single-sided deaf (SSD) CI users prefer to listen to music with the acoustic hearing (AH) and CI ears together rather than with the AH ear alone. The source of this binaural benefit remains unclear. In the present study, sound quality ratings were collected in SSD CI users for music excerpts from different genres (pop, rock, and classical). A novel vocoder-to-the-CI (VCI) approach was used to control the spectral and temporal information delivered to the CI ear. Custom sine-wave vocoders were designed for each participant according to the frequency allocation in their clinical map. Sound quality ratings were collected with CI-only, AH-only, and CI+AH listening. CI+AH ratings were significantly higher than AH-only ratings when unprocessed stimuli or vocoded stimuli with spectro-temporal information were delivered to the CI ear. There were no significant differences among CI+AH ratings for the unprocessed stimuli, vocoded stimuli with spectro-temporal information, and vocoded stimuli with greatly reduced temporal cues, suggesting that the binaural benefit was largely driven by similar spectral information across ears. Effects of genre were minimal. CI+AH ratings for unprocessed music were significantly correlated with CI-only ratings (r = 0.57, p < 0.001), with the slope (0.97) suggesting that the binaural benefit was largely additive between the AH and CI ears. VCI appears to be a fruitful approach to control the spectral and temporal information delivered to the CI ear without directly manipulating CI users’ clinical processors.

尽管人工耳蜗（CIs）提供的音质较差，但单侧耳聋（SSD） CI用户更喜欢用声学听力（AH）和CI耳朵一起听音乐，而不是单独使用AH耳朵。这种双耳益处的来源尚不清楚。在本研究中，我们收集了SSD CI用户对不同类型音乐（流行、摇滚和古典）的音质评分。提出了一种新的声码器-声码器（VCI）方法来控制传递到声码器耳的频谱和时间信息。根据临床图谱中的频率分配，为每位参与者设计定制的正弦波声码器。通过仅CI、仅AH和CI+AH收听收集音质评分。当将未经处理的刺激或带有光谱时间信息的声音编码刺激传递到CI耳时，CI+AH评分明显高于AH评分。未处理的刺激、带有光谱-时间信息的声编码刺激和时间线索大大减少的声编码刺激的CI+AH评分无显著差异，表明双耳获益主要是由双耳间相似的频谱信息驱动的。体裁的影响很小。未处理音乐的CI+AH评分与仅CI评分显著相关（r = 0.57, p < 0.001），斜率（0.97）表明双耳收益在很大程度上是AH和CI耳朵之间的相加性。VCI似乎是一种有效的方法来控制传递到CI耳的频谱和时间信息，而无需直接操纵CI用户的临床处理器。

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引用次数: 0

Differences in hearing across the lifespan in two strains of Alzheimer’s mouse models as measured using behavioral and physiological techniques 使用行为和生理技术测量两种阿尔茨海默氏症小鼠模型在整个生命周期中的听力差异。

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-01-29 DOI: 10.1016/j.heares.2026.109550

Payton E. Charlton , Kali Burke , Sevda Abdavinejad , Mariam Ashour , Zachary Zaharkin , Riley McLaughlin , Srijita Paul , Amanda M. Lauer , Micheal L. Dent

Alzheimer’s disease (AD) is a brain condition with heterogeneity in disease progression due to genetic and environmental variables. There is a critical need to better understand the relationship of AD pathologies and potential modifiable factors like hearing loss. Auditory processing measurements in AD mouse models have been reported, but the results are mixed. Most were conducted using evoked potential recordings measured under anesthesia, unlike typical hearing assessments on aging adult humans. Here, we used operant conditioning and signal detection theory to measure daily pure tone behavioral detection throughout the lifespan of trained mutant and wild-type (WT) control APP/PS1 (on a C57BL/6J background) and 5xFAD (on a C57/SJL background) mice. At the conclusion of operant testing, auditory brainstem response (ABR) measures were taken on the same subjects to determine if evoked potentials provided accurate estimates of perceptual abilities. Behavioral detection worsened significantly across the lifespan in APP/PS1 mice, but there were no differences between mutant and WT mice. For 5xFAD mice, behavioral thresholds generally worsened over the lifespan but with substantial variability, which may be explained by genetic heterogeneity among the background strain. There were no differences between 5xFAD mutant and WT mice. ABR hearing threshold estimates generally matched behavioral findings, with APP/PS1 having significantly worse thresholds than 5xFAD mice but no within-model differences between mutants and WTs. The within-subject differences between behavioral and ABR thresholds ranged from <1 dB to over 40 dB across subjects, suggesting physiological measurements of auditory function are not necessarily reflective of an animal’s acoustic perception.

阿尔茨海默病（AD）是一种由于遗传和环境变量导致疾病进展异质性的脑部疾病。我们迫切需要更好地了解阿尔茨海默病病理与听力损失等潜在可改变因素的关系。已经报道了AD小鼠模型的听觉处理测量，但结果好坏参半。大多数是在麻醉下使用诱发电位记录进行的，不像对老年人进行典型的听力评估。在这里，我们使用操作性条件反射和信号检测理论来测量训练突变型和野生型（WT）对照APP/PS1 （C57BL/6J背景）和5xFAD （C57/SJL背景）小鼠在整个生命周期中的每日纯音行为检测。在操作性测试结束后，对同一受试者进行听觉脑干反应（ABR）测量，以确定诱发电位是否能准确估计感知能力。APP/PS1小鼠的行为检测在整个生命周期中显著恶化，但突变小鼠和WT小鼠之间没有差异。对于5xFAD小鼠，行为阈值在整个生命周期中普遍恶化，但存在很大的变异性，这可能是由背景菌株之间的遗传异质性解释的。5xFAD突变体与WT小鼠无差异。ABR听力阈值估计值通常与行为发现相匹配，APP/PS1的阈值明显低于5xFAD小鼠，但突变体和WTs之间没有模型内差异。行为阈值和ABR阈值之间的主体内差异从

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引用次数: 0

Psychoacoustic and cognitive predictors of sound sensitivity in healthy young adults 健康年轻人声音敏感性的心理声学和认知预测因素。

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-01-28 DOI: 10.1016/j.heares.2026.109549

Breann Krygsman, Alisa Pitre, Sebastien Paquette

Hyperacusis and sound sensitivity are complex phenomena influenced by both auditory and psychological factors. This study investigated the relationship between hearing thresholds, perceptual ratings of natural sounds, attitudes toward noise, and sex-based differences in a sample of healthy young adults. Fifty participants underwent pure-tone audiometry, completed a psychoacoustic test assessing hyperacusis (sound sensitivity), and filled out self-report questionnaires including the Youth Attitudes to Noise Scale (YANS) and the Beliefs About Hearing Protection and Hearing Loss (BAHPHL). Contrary to expectations, greater sound sensitivity was associated with lower hearing thresholds (indicating minimal hearing loss) in the low-frequency range. This suggests that preserved low-frequency hearing may contribute to auditory discomfort. Questionnaire data revealed that individuals with higher sound sensitivity also held more negative beliefs about noise and hearing protection, highlighting the role of cognitive and affective factors. No significant sex differences were found, though prior research suggests biological distinctions may still influence auditory processing. These findings underscore the importance of considering both perceptual and psychological dimensions in understanding hyperacusis.

听觉亢进和声敏感是受听觉和心理因素共同影响的复杂现象。本研究调查了健康年轻人的听力阈值、对自然声音的感知等级、对噪音的态度和性别差异之间的关系。50名参与者接受了纯音听力学测试，完成了评估听觉过敏（声音敏感性）的心理声学测试，并填写了自我报告问卷，包括青少年对噪音的态度量表（YANS）和关于听力保护和听力损失的信念（BAHPHL）。与预期相反，在低频范围内，更高的声音灵敏度与较低的听力阈值（表明听力损失最小）相关。这表明保留的低频听力可能导致听觉不适。问卷调查数据显示，声音敏感度高的个体对噪音和听力保护的负面看法也更多，这突出了认知和情感因素的作用。没有发现明显的性别差异，尽管先前的研究表明生物差异仍然可能影响听觉处理。这些发现强调了在理解听觉亢进时考虑知觉和心理两方面的重要性。

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引用次数: 0

Pbx1 overexpression delays cochlear hair cells degeneration in an accelerated aging mouse model Pbx1过表达延缓了加速衰老小鼠耳蜗毛细胞的退化

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-01-20 DOI: 10.1016/j.heares.2026.109546

Ruihan Zhu , Gaogan Jia , Yiming Shen , Xian Gao , Yunjie Li , Hua Jiang , Hui Chai , Mingyu Xia

Age-related hearing loss (ARHL), the most prevalent sensory disorder worldwide, arises primarily from cochlear hair cells (HCs) degeneration due to aging. Although the molecular mechanisms driving HC senescence are increasingly understood, effective treatments for ARHL remain lacking. This study explores the therapeutic potential role of Pre-B cell leukemia homeobox 1 (Pbx1), a transcription factor involved in inner ear development and pluripotency, in mitigating ARHL. Our results reveal a striking age-dependent reduction in PBX1 expression within mouse cochlear HCs. Using D-galactose (D-gal)/lipopolysaccharide (LPS)-induced aging models in OC-1 cells and cultured cochlear explants, we demonstrated that lentiviral and adeno-associated virus (AAV)-mediated Pbx1 overexpression significantly suppresses senescent markers and preserves HC integrity. Remarkably, in vivo delivery of Pbx1 by AAV improved auditory function and preserved HC structure and function in ARHL mouse model. These results establish Pbx1 as a key mediator of HC aging and a promising therapeutic target for ARHL. Our findings demonstrate that AAV-mediated Pbx1 overexpression represents a potential therapeutic approach to prevent ARHL progression, paving the way for future clinical management of this prevalent sensory disorder.

年龄相关性听力损失（ARHL）是世界上最常见的感觉障碍，主要由耳蜗毛细胞（hc）老化引起的变性引起。尽管人们对HC衰老的分子机制越来越了解，但ARHL的有效治疗方法仍然缺乏。本研究探讨了前b细胞白血病同源盒1 （Pbx1）在缓解ARHL中的潜在治疗作用，Pbx1是一种参与内耳发育和多能性的转录因子。我们的研究结果揭示了小鼠耳蜗hc中PBX1表达的显著年龄依赖性减少。利用d -半乳糖(D-gal)/脂多糖（LPS）诱导的OC-1细胞和人工耳蜗外体衰老模型，我们证明了慢病毒和腺相关病毒（AAV）介导的Pbx1过表达显著抑制衰老标志物并保持HC完整性。在ARHL小鼠模型中，通过AAV给药Pbx1显著改善了听觉功能，并保留了HC结构和功能。这些结果表明，Pbx1是HC衰老的关键介质，也是ARHL的一个有希望的治疗靶点。我们的研究结果表明，aav介导的Pbx1过表达代表了一种预防ARHL进展的潜在治疗方法，为这种普遍感觉障碍的未来临床管理铺平了道路。

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引用次数: 0

Bayesian simulation of hearing thresholds at conventional and extended high frequencies in young adults 年轻人常规高频和扩展高频听力阈值的贝叶斯模拟。

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-01-20 DOI: 10.1016/j.heares.2026.109547

N. Shahnaz, V. Ciocca

The goal of this study was to characterize the population-level distributions of hearing thresholds at conventional and extended high frequencies (EHFs). To achieve this goal, distributions of typical hearing thresholds expressed in dB SPL were measured in an otologically normal young-adult sample. Thresholds were obtained using an adaptive procedure with the Sennheiser HDA-200 earphone. Thresholds were measured at 16 frequencies, ranging from 250 Hz to 16 kHz, in a non-random sample of 126 young adults (18-36 years old) with typical hearing (≤ 20 dB HL at conventional frequencies). Using the posterior of a Bayesian multilevel distributional regression model that was fit to the data, we simulated hearing thresholds at conventional and extended high frequencies for 18,000 new participants. The simulated thresholds were used to calculate probabilistic estimates of the reference equivalent threshold sound pressure levels (RETSPLs) and other percentiles of the distributions of hearing thresholds at each frequency. We used these percentile estimates to define the range of typical hearing sensitivity in dB SPL and found that this range varies across frequency, unlike the current fixed 20–25 dB HL cutoffs that are used to classify “normal” hearing. Specifically, at conventional frequencies, the fixed 20–25 dB HL cutoffs overestimated the range of typical thresholds, whereas at extended high frequencies, the fixed cutoffs overestimated this range. The proposed probabilistic approach provides a framework for characterizing the information from pure tone thresholds in terms of the range of hearing sensitivity, rather than categorizing hearing ability on the basis of a frequency-invariant criterion.

本研究的目的是表征常规高频和扩展高频（EHFs）听力阈值的人群水平分布。为了实现这一目标，我们在一个耳部正常的年轻人样本中测量了以分贝声压级表达的典型听力阈值的分布。使用Sennheiser HDA-200耳机采用自适应程序获得阈值。在126名听力正常（常规频率≤20 dB HL）的年轻人（18-36岁）的非随机样本中，测量了从250 Hz到16 kHz的16个频率的阈值。使用拟合数据的贝叶斯多水平分布回归模型的后验，我们模拟了18,000名新参与者在常规高频和扩展高频下的听力阈值。模拟阈值用于计算每个频率下参考等效阈值声压级（RETSPLs）和听力阈值分布的其他百分位数的概率估计。我们使用这些百分位数估计值来定义以dB SPL为单位的典型听力灵敏度范围，并发现该范围随频率而变化，而不像目前用于分类“正常”听力的固定20-25 dB HL截止值。具体来说，在常规频率下，固定的20-25 dB HL截止值高估了典型阈值的范围，而在扩展的高频下，固定截止值高估了该范围。所提出的概率方法提供了一个框架，根据听觉灵敏度的范围来描述来自纯音阈值的信息，而不是根据频率不变标准对听觉能力进行分类。

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引用次数: 0

A primate model revealed specific age-related changes in spiral ganglion neurons in the cochlea 灵长类动物模型揭示了耳蜗螺旋神经节神经元的特定年龄相关变化。

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-01-18 DOI: 10.1016/j.heares.2026.109545

Masafumi Ueno , Makoto Hosoya , Marie N Shimanuki , Takanori Nishiyama , Naoki Oishi , Hiroyuki Ozawa

Type I spiral ganglion neurons, which play a major role in hearing by conveying electrical sound signals to the brain, are divided into electrophysiological and molecular subtypes. The differences in vulnerability among the subtypes reported in rodents are of pathophysiological importance for age-related hearing loss. However, the changes in spiral ganglion neurons in primates and humans have not been established. In this study, we investigated the age-related changes in the spiral ganglion neurons of the common marmoset, a primate model animal. Here, we show that the overall number of spiral ganglion neurons decreased in middle-aged individuals and was most pronounced during the basal turn. However, no subtype-specific reduction, as reported in rodents, was identified. Our observations indicate that aging-related changes observed in the cochlea of rodents are not always applicable to primates. The usefulness and importance of common marmosets in the study of age-related hearing loss are also highlighted.

I型螺旋神经节神经元通过向大脑传递电信号在听觉中起主要作用，分为电生理亚型和分子亚型。在啮齿动物中报告的易损性亚型之间的差异对年龄相关性听力损失具有病理生理学意义。然而，灵长类动物和人类螺旋神经节神经元的变化尚未确定。在这项研究中，我们研究了普通狨猴螺旋神经节神经元的年龄相关变化，这是一种灵长类模型动物。在这里，我们发现螺旋神经节神经元的总数在中年个体中减少，并且在基底转期间最为明显。然而，在啮齿类动物中，没有发现特异性亚型的减少。我们的观察表明，在啮齿动物耳蜗中观察到的与衰老相关的变化并不总是适用于灵长类动物。本文还强调了普通狨猴在年龄相关性听力损失研究中的实用性和重要性。

引用次数: 0

Noise exposure induces autophagy-modulated nuclear-to-cytoplasmic translocation of TDP-43 in spiral ganglion neurons 噪声暴露诱导自噬调节的螺旋神经节神经元TDP-43向胞质转运

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-01-15 DOI: 10.1016/j.heares.2026.109544

Rong Han , Yefei Mo , Lingxiao Jiang , Junsheng Hong , Zhiqi Mao , Yang Li , Menghua Li , Ke Liu , Yuhe Liu

Noise exposure contributes to approximately one-third of hearing loss cases worldwide. Despite its substantial global burden, noise-induced hearing loss (NIHL) remains essentially irreversible, largely because its underlying pathogenic mechanisms are not yet fully defined. In this study, we established three noise-induced hearing loss mouse models and evaluated auditory function by measuring auditory brainstem response (ABR) thresholds at multiple time points following noise exposure. In parallel, we examined the spatiotemporal redistribution of TDP-43 and evaluated autophagic flux in spiral ganglion neurons (SGNs) to elucidate their dynamic responses to acoustic stress. Noise exposure triggers marked nucleocytoplasmic translocation and cytoplasmic aggregation of TDP-43 in spiral ganglion neurons (SGNs), accompanied by dynamic alterations in autophagic flux. Using pharmacological modulation, we demonstrate that autophagy critically shapes the fate of TDP-43. Mechanistically, noise-induced stressors such as reactive oxygen species (ROS) likely initiate TDP-43 nuclear export, whereas insufficient autophagic flux impedes aggregate degradation and exacerbates cytoplasmic inclusion formation. Together, these findings reveal autophagy as a key determinant of TDP-43 dynamics in the auditory system and identify the autophagy–TDP-43 axis as a potential therapeutic target for preventing or ameliorating noise-induced hearing loss.

全球约三分之一的听力损失病例是由噪音造成的。尽管噪声性听力损失（NIHL）给全球带来了沉重的负担，但它基本上是不可逆转的，这主要是因为其潜在的致病机制尚未完全确定。在本研究中，我们建立了三种噪声性听力损失小鼠模型，并通过测量噪声暴露后多个时间点的听觉脑干反应（ABR）阈值来评估听觉功能。同时，我们检测了TDP-43的时空分布，并评估了螺旋神经节神经元（SGNs）的自噬通量，以阐明它们对声应力的动态响应。噪声暴露触发螺旋神经节神经元（SGNs）中显著的核胞质易位和胞质TDP-43聚集，并伴有自噬通量的动态改变。通过药理调节，我们证明自噬对TDP-43的命运起着至关重要的作用。在机制上，噪声诱导的应激源如活性氧（ROS）可能启动TDP-43核输出，而自噬通量不足阻碍了聚集体降解并加剧了细胞质包涵体的形成。总之，这些发现揭示了自噬是听觉系统中TDP-43动力学的关键决定因素，并确定了自噬- TDP-43轴作为预防或改善噪声性听力损失的潜在治疗靶点。

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引用次数: 0

New concept for mechanisms of hair cell regeneration in the chick auditory epithelium 鸡听觉上皮毛细胞再生机制新认识

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-01-14 DOI: 10.1016/j.heares.2026.109543

Marie Takeuchi, Mami Matsunaga, Takayuki Nakagawa

Sensory hair cells in the cochlea are essential for hearing. In adult mammals, hair cells are incapable of regeneration, primarily because the supporting cells lose their regenerative capacity shortly after birth. In contrast, avian supporting cells maintain a remarkable ability to regenerate hair cells throughout their lifespan. Two distinct regenerative pathways are activated following damage: proliferation of supporting cells, followed by differentiation or their direct conversion into new hair cells. The specific molecular mechanisms governing these pathways and the factors determining which behavior (mitosis or direct conversion) the supporting cells adopt remain largely elusive. Elucidating the molecular mechanisms underlying this natural regeneration process in the avian cochlea may offer crucial insights into inducing hair cell regeneration in the mature mammalian inner ear. This review summarizes the current understanding of how supporting cells naturally replace lost hair cells in the chick cochlea.

耳蜗中的感觉毛细胞对听力至关重要。在成年哺乳动物中，毛细胞是不能再生的，主要是因为支持细胞在出生后不久就失去了再生能力。相比之下，鸟类的支持细胞在其整个生命周期中都保持着再生毛细胞的非凡能力。两种不同的再生途径在受损后被激活：支持细胞增殖，随后分化或直接转化为新的毛细胞。控制这些途径的特定分子机制和决定支持细胞采取何种行为（有丝分裂或直接转化）的因素在很大程度上仍然难以捉摸。阐明鸟类耳蜗自然再生过程的分子机制可能为诱导成熟哺乳动物内耳毛细胞再生提供重要见解。这篇综述总结了目前对支持细胞如何自然替换小鸡耳蜗中丢失的毛细胞的理解。

引用次数: 0