Hearing Research最新文献

{"title":"Uncovering cellular senescence as a therapeutic target in NF2-related vestibular schwannoma","authors":"Sandra Franco-Caspueñas ,&nbsp;Carmen García-Montoya ,&nbsp;Julio Contreras ,&nbsp;Luis Lassaletta ,&nbsp;Isabel Varela-Nieto ,&nbsp;Ana M. Jiménez-Lara","doi":"10.1016/j.heares.2024.109165","DOIUrl":"10.1016/j.heares.2024.109165","url":null,"abstract":"<div><h3>Background</h3><div>Vestibular schwannomas (VS) are complex and heterogeneous human tumors arising from the Schwann cell compartment of the vestibulocochlear nerve. VS cause significant neurological deficit such as hearing loss and vestibular impairment, and in some cases death due to brainstem compression. There is an urgent need to find pharmacotherapies for VS since surgical removal and stereotactic radiosurgery are the only effective treatments. Cancer therapy based in the combination of drug-induced senescence and senolytics may provide an innovative pharmacological alternative for VS management.</div></div><div><h3>Methods</h3><div>Senescence-associated β-galactosidase (SA-β-GAL) activity detection assay, real-time polymerase chain reaction (RT-PCR), western blotting and immunofluorescence, together with viability assays were used to analyze the response to different chemotherapy drugs of the human VS HEI-193 cell line. Human VS tumor paraffin sections were also studied for SA-β-GAL-stained cells.</div></div><div><h3>Results</h3><div>We found that chemotherapy compounds induced genotoxic stress and cellular senescence in HEI-193 VS cells, as characterized by increased SA-β-GAL activity, growth arrest, increased levels of the cyclin-dependent kinase inhibitor p21 and the accumulation of DNA damage. These cellular senescence markers were also accompanied by an increase of senescence-associated secretory phenotype (SASP): <em>IL6, IL8, IL1B</em> and <em>MMP1</em>. Induction of senescence by chemotherapy rendered HEI-193 VS cells as druggable targets for senolytic compounds, as navitoclax. Thus, treatment with navitoclax selectively eliminated bleomycin-induced senescent HEI-193 VS cells by activating the extrinsic and intrinsic apoptosis pathways. Our data also show the presence of senescent cells, SA-β-GAL-positive stain, in human VS tumors, which are not present in healthy great auricular nerve sections.</div></div><div><h3>Conclusions</h3><div>These findings suggest that a one-two punch strategy of pro-senescence therapy induced by chemotherapy treatment followed by senolytic therapy represents a new paradigm for the pharmacological treatment of VS.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"455 ","pages":"Article 109165"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hearing Research: Departing Editorial from your Resigning Editor-in-Chief, Barbara Canlon","authors":"Barbara Canlon","doi":"10.1016/j.heares.2024.109168","DOIUrl":"10.1016/j.heares.2024.109168","url":null,"abstract":"","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"455 ","pages":"Article 109168"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why does tinnitus vary with naps? A polysomnographic prospective study exploring the somatosensory hypothesis","authors":"Robin Guillard ,&nbsp;Vincent Philippe ,&nbsp;Adam Hessas ,&nbsp;Brice Faraut ,&nbsp;Sarah Michiels ,&nbsp;Minchul Park ,&nbsp;Marco Congedo ,&nbsp;Alain Londero ,&nbsp;Damien Léger","doi":"10.1016/j.heares.2024.109152","DOIUrl":"10.1016/j.heares.2024.109152","url":null,"abstract":"<div><h3>Background</h3><div>Tinnitus, defined as the conscious awareness of a noise without any identifiable corresponding external acoustic source, can be modulated by various factors. Among these factors, tinnitus patients commonly report drastic increases of tinnitus loudness following nap sleep. Previous studies have suggested that this clinical pattern could be attributed to a somatosensory modulation of tinnitus. To our knowledge, no polysomnographic study has been carried out to assess this hypothesis.</div></div><div><h3>Methods</h3><div>For this observational prospective study, 37 participants reporting frequent increases of tinnitus following naps were recruited. They participated to six full-polysomnography nap attempts over two days. Audiological and kinesiologic tests were conducted before and after each nap attempt.</div></div><div><h3>Results</h3><div>197 naps were collected. Each nap at each time of day elicited an overall significant increase in tinnitus minimum masking level (MML). Each inter nap period elicited an overall significant decrease. Tinnitus modulations were found significantly correlated with nap sleep duration (Visual numeric scale on tinnitus loudness, VNS-L, <em>p</em> &lt; 0.05), with snoring duration (MML, <em>p</em> &lt; 0.001), with snoring average sound level (VNS on tinnitus intrusiveness, VNS-I, <em>p</em> &lt; 0.05) and with sleep apnea count (VNS-I, <em>p</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>This study confirms objectively that tinnitus may increase following naps. No association was found between these modulations and somatosensory modulations involving the temporomandibular joint and cervical areas. However, it may be possible that nap-induced tinnitus modulations are a hidden form of somatosensory modulation as snoring and sleep apnea events are often related to tensor veli palatini muscle dysfunction.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"455 ","pages":"Article 109152"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visualizing motions within the cochlea's organ of Corti and illuminating cochlear mechanics with optical coherence tomography","authors":"Elizabeth S. Olson ,&nbsp;Wei Dong ,&nbsp;Brian E. Applegate ,&nbsp;Karolina K. Charaziak ,&nbsp;James B. Dewey ,&nbsp;Brian L. Frost ,&nbsp;Sebastiaan W.F. Meenderink ,&nbsp;Jong-Hoon Nam ,&nbsp;John S. Oghalai ,&nbsp;Sunil Puria ,&nbsp;Tianying Ren ,&nbsp;C. Elliott Strimbu ,&nbsp;Marcel van der Heijden","doi":"10.1016/j.heares.2024.109154","DOIUrl":"10.1016/j.heares.2024.109154","url":null,"abstract":"<div><div>Beginning in 2006, optical coherence tomography (OCT) has been adapted for use as a vibrometer for hearing research. The application of OCT in this field, particularly for studying cochlear mechanics, represents a revolutionary advance over previous technologies. OCT provides detailed evidence of the motions of components within the organ of Corti, extending beyond the first-encountered surface of observation. By imaging through the bony capsule as well as through the round window membrane, OCT has measured vibration at multiple locations along the cochlear spiral, in vivo, under nearly natural conditions. In this document, we present examples of recent research findings to illustrate the applications of OCT in studying cochlear mechanics in both normal and impaired ears.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"455 ","pages":"Article 109154"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hearing Research: Introduction of Manuel S. Malmierca as the new Editor-in-Chief","authors":"Manuel S. Malmierca","doi":"10.1016/j.heares.2024.109169","DOIUrl":"10.1016/j.heares.2024.109169","url":null,"abstract":"","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"455 ","pages":"Article 109169"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signal-in-noise detection across the lifespan in a mouse model of presbycusis","authors":"Dimitri L. Brunelle ,&nbsp;Collin R. Park ,&nbsp;Timothy J. Fawcett ,&nbsp;Joseph P. Walton","doi":"10.1016/j.heares.2024.109153","DOIUrl":"10.1016/j.heares.2024.109153","url":null,"abstract":"<div><div>The auditory system is constantly tasked with detecting acoustic cues in complex auditory environments. Difficulty hearing speech in noise, largely a result of energetic masking, is a major communication complaint of the elderly, which impacts a third of the global population over 65. The neural mechanisms responsible for processing sound in background noise and subsequently achieving release from energetic masking remain obscure. Furthermore, the senescence of signal-in-noise detection is poorly understood, a phenomenon which could have a myriad of clinical implications. We tested over 300 CBA/CaJ mice aged 1–27 months on tone-in-noise detection ability utilizing prepulse inhibition of the acoustic startle response with a machine learning startle classifier. We found that mice developed profound tone-in-noise detection deficits throughout their lifespan as evidenced by <em>Rd′</em>, a detection metric derived from signal detection theory. The most severe decline in <em>Rd′</em> corresponded to a 2.54-fold decrease in tone-in-noise detection across the lifespan. Our findings suggest that CBA/CaJ mice are an appropriate model to study the role of age-related hearing loss in the context of signal-in-noise masking.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"455 ","pages":"Article 109153"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extent of genetic and epigenetic factor reprogramming via a single viral vector construct in deaf adult mice","authors":"Niliksha Gunewardene ,&nbsp;Patrick Lam ,&nbsp;Jiwei Song ,&nbsp;Trung Nguyen ,&nbsp;Shannon Mendez Ruiz ,&nbsp;Raymond C.B. Wong ,&nbsp;Andrew K. Wise ,&nbsp;Rachael T. Richardson","doi":"10.1016/j.heares.2024.109170","DOIUrl":"10.1016/j.heares.2024.109170","url":null,"abstract":"<div><div>In the adult mammalian cochlea, hair cell loss is irreversible and causes deafness. The basic helix-loop transcription factor Atoh1 is essential for normal hair cell development in the embryonic ear. Over-expression of Atoh1 in the adult cochlea by gene therapy can convert supporting cells (cells that underlie hair cells) into a hair cell lineage. However, the regeneration outcomes can be inconsistent. Given that hair cell development is regulated by multiple signalling and transcriptional factors in a temporal and spatial manner, a more complex combinatorial approach targeting additional transcription factors may be required for efficient hair cell regeneration. There is evidence that epigenetic factors are responsible for the lack in regenerative capacity of the deaf adult cochlea. This study aimed to develop a combined gene therapy approach to reprogram both the genome and epigenome of supporting cells to improve the efficiency of hair cell regeneration. Adult Pou4f3-DTR mice were used in which the administration of diphtheria toxin was used to ablate hair cells whilst leaving supporting cells relatively intact. A single adeno-associated viral construct was used to express human Atoh1, Pou4f3 and short hairpin RNA against Kdm1a (regeneration gene therapy) at two weeks following partial or severe hair cell ablation. The average transduction of the inner supporting cells, as measured by the control AAV2.7m8-GFP vector in the deaf cochlea, was only 8 % while transduction in the outer sensory region was &lt;1 %. At 4- and 6-weeks post-treatment the number of Myo+ hair cells in the control and regeneration gene therapy-treated mice were not significantly different. Of note, although both control and regeneration gene therapy treated cochleae contained supporting cells that co-expressed the hair cell marker Myo7a and the supporting cell marker Sox2, the regeneration gene therapy treated cochleae had significantly higher numbers of these cells (<em>p</em> &lt; 0.05). Furthermore, among these treated cochleae, those that had more hair cell loss had a higher number of Myo7a positive supporting cells (R2=0.33, Pearson correlation analysis, <em>p</em> &lt; 0.001). Overall, our results indicate that the adult cochlea possesses limited intrinsic spontaneous regenerative capacity, that can be further enhanced by genetic and epigenetic reprogramming.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"457 ","pages":"Article 109170"},"PeriodicalIF":2.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemispheric difference of adaptation lifetime in human auditory cortex measured with MEG","authors":"Asim H. Dar ,&nbsp;Nina Härtwich ,&nbsp;Aida Hajizadeh ,&nbsp;Michael Brosch ,&nbsp;Reinhard König ,&nbsp;Patrick J.C. May","doi":"10.1016/j.heares.2024.109173","DOIUrl":"10.1016/j.heares.2024.109173","url":null,"abstract":"<div><div>Adaptation is the attenuation of a neuronal response when a stimulus is repeatedly presented. The phenomenon has been linked to sensory memory, but its exact neuronal mechanisms are under debate. One defining feature of adaptation is its lifetime, that is, the timespan over which the attenuating effect of previous stimulation persists. This can be revealed by varying the stimulus-onset interval (SOI) of the repeated stimulus. As SOI is increased, the peak amplitude of the response grows before saturating at large SOIs. The rate of this growth can be quantified and used as an estimate of adaptation lifetime. Here, we studied whether adaptation lifetime varies across the left and the right auditory cortex of the human brain. Event-related fields of whole-head magnetoencephalograms (MEG) were measured in 14 subjects during binaural presentation of pure tone stimuli. To make statistical inferences on the single-subject level, additional event-related fields were generated by resampling the original single-trial data via bootstrapping. For each hemisphere and SOI, the peak amplitude of the N1m response was then derived from both original and bootstrap-based data sets. Finally, the N1m-peak amplitudes were used for deriving subject- and hemisphere-specific estimates of adaptation lifetime. Comparing subject-specific adaptation lifetime across hemispheres, we found a significant difference, with longer adaptation lifetimes in the left than in the right auditory cortex (<em>p</em> = 0.004). This difference might have a functional relevance in the context of temporal binding of auditory stimuli, leading to larger integration time windows in the left than in the right hemisphere.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"458 ","pages":"Article 109173"},"PeriodicalIF":2.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene therapy for hereditary hearing loss","authors":"Zeming Fu ,&nbsp;Liping Zhao ,&nbsp;Yingyuan Guo ,&nbsp;Jingpu Yang","doi":"10.1016/j.heares.2024.109151","DOIUrl":"10.1016/j.heares.2024.109151","url":null,"abstract":"<div><div>Gene therapy is a technique by which exogenous genetic material is introduced into target cells to treat or prevent diseases caused by genetic mutations. Hearing loss is the most common sensory disorder. Genetic factors contribute to approximately 50 % of all cases of profound hearing loss, and more than 150 independent genes have been reported as associated with hearing loss. Recent advances in CRISPR/Cas based gene-editing tools have facilitated the development of gene therapies for hereditary hearing loss (HHL). Viral delivery vectors, and especially adeno-associated virus (AAV) vectors, have been demonstrated as safe and efficient carriers for the delivery of transgenes into inner ear cells in animal models. More importantly, AAV-mediated gene therapy can restore hearing in some children with hereditary deafness. However, there are many different types of HHL that need to be identified and evaluated to determine appropriate gene therapy options. In the present review, we summarize recent animal model-based advances in gene therapy for HHL, as well as gene therapy strategies, gene-editing tools, delivery vectors, and administration routes. We also discuss the strengths and limitations of different gene therapy methods and describe future challenges for the eventual clinical application of gene therapy for HHL.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"455 ","pages":"Article 109151"},"PeriodicalIF":2.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The therapeutic effect and underlying biochemical mechanism of methylprednisolone and D-methionine in “rescuing” noise-induced hearing loss in guinea pigs","authors":"Po-Hsuan Wu ,&nbsp;Wu-Chia Lo ,&nbsp;Chih-Ming Chang ,&nbsp;Po-Wen Cheng ,&nbsp;Shing-Hwa Liu","doi":"10.1016/j.heares.2024.109148","DOIUrl":"10.1016/j.heares.2024.109148","url":null,"abstract":"<div><h3>Objectives</h3><div>Currently, there are no approved therapeutics for noise-induced hearing loss (NIHL). Both oxidative stress and cochlear inflammation play important roles in the mechanism of NIHL. In this study, we evaluate the effect of D-methionine (D-met) and methylprednisolone (MP) on noise-induced hearing loss of guinea pigs.</div></div><div><h3>Design</h3><div>One hundred and thirty-two male guinea pigs were evenly divided into eleven groups: control, saline, MP (15, 30, 45 mg/kg), D-met (200, 400, 600 mg/kg), and combinations of MP (15, 30, 45 mg/kg) with D-met (200, 400, 600 mg/kg) in increasing doses. Sixty minutes following a 6-hour exposure to continuous broadband white noise at a sound pressure level of 105 ± 2 dB, treatments were given every 12 h over the course of 3 days. Click-evoked auditory brainstem responses were evaluated one day before and fourteen days after noise exposure. The animals in the combination group were sacrificed 14 days after noise exposure, and cochlear lateral wall Na⁺, K⁺-ATPase and Ca²⁺-ATPase activities, and lipid peroxidation (LPO) were evaluated.</div></div><div><h3>Results</h3><div>The mean permanent threshold shift (PTS) showed a dose-dependent rescue effect from low to high doses in both MP and D-met treatment groups. In the combination treatment groups, MP (45 mg/kg) with D-met (600 mg/kg) demonstrated a complete rescue response without a significant difference in PTS compared to the control group. The noise-induced decreases in Na⁺, K⁺-ATPase and Ca²⁺-ATPase activities demonstrated dose-dependent recoveries from the low to high dose combination groups. Specifically, the MP (45 mg/kg) with D-met (600 mg/kg) group achieved 84.8% and 95.5% recovery of Na⁺, K⁺-ATPase and Ca²⁺-ATPase activity levels, respectively, compared to the control group. The noise-induced increase in LPO levels exhibited dose-dependent alleviation from the low to high dose combination groups, showing only a 12.3% LPO increment in the MP (45 mg/kg) with D-met (600 mg/kg) group.</div></div><div><h3>Conclusions</h3><div>Noise-induced hearing loss was completely rescued in the MP (45 mg/kg) with D-met (600 mg/kg) treatment group. Significant decreases in cochlear lateral wall oxidative stress were demonstrated, along with the reversal of Na⁺, K⁺-ATPase and Ca²⁺-ATPase activity levels.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"454 ","pages":"Article 109148"},"PeriodicalIF":2.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}