Hearing Research最新文献

{"title":"Insulin-like growth factor 1 protects cochlear outer hair cells against cisplatin","authors":"Kohei Yamahara ,&nbsp;Hiroe Ohnishi ,&nbsp;Takayuki Nakagawa ,&nbsp;Koichi Omori ,&nbsp;Norio Yamamoto","doi":"10.1016/j.heares.2025.109287","DOIUrl":"10.1016/j.heares.2025.109287","url":null,"abstract":"<div><div>Cisplatin<strong>,</strong> an effective anti-neoplastic drug widely used in oncology protocols, has an adverse effect such as ototoxicity, for which no current treatment exists. Histological lesions in the cochlea after cisplatin administration are most prominent in outer hair cells in the organ of Corti. We have previously reported that insulin-like growth factor 1 (IGF1) protects cochlear hair cells (HCs) against several types of damage to the cochlea, including noise exposure, ischemia, surgical trauma, and aminoglycoside, resulting in hearing recovery. In the present study, we investigated the efficacy of IGF1 as a molecule to protect inner ear auditory sensory HCs against cisplatin using cochlear explant culture systems of postnatal day 2 mice. Administration of IGF1 to the explants grown in the medium containing cisplatin markedly protected outer HCs from cisplatin-induced damage. Pharmacological inhibition of IGF1 receptor (IGF1R) using an IGF1R antagonist or inhibitor markedly attenuated the protective activity of IGF1, indicating that IGF1R is specifically required for IGF1 effects in HCs against cisplatin. As a protective mechanism against cisplatin, we found that the administration of IGF1 reduces cisplatin-induced oxidative stress. IGF1 effects on the maintenance of HC numbers are achieved by inhibiting the apoptosis of HCs, not by inducing the proliferation of HCs or supporting cells (SCs). We conclude that treatment with IGF1 could be an efficient and safe approach to treat cisplatin-induced ototoxicity.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"463 ","pages":"Article 109287"},"PeriodicalIF":2.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907568","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":"Comparative approaches to investigate the principles of hearing","authors":"Christine Köppl ,&nbsp;Sonja J. Pyott","doi":"10.1016/j.heares.2025.109286","DOIUrl":"10.1016/j.heares.2025.109286","url":null,"abstract":"","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"462 ","pages":"Article 109286"},"PeriodicalIF":2.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965491","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":"Axon terminal distribution in layer 1 of the mouse auditory cortex: differential projections from the dorsal and medial subdivisions of the medial geniculate body and the marginal zone of the posterior thalamic nuclei","authors":"Meng Sun ,&nbsp;Makoto Takemoto ,&nbsp;Ryohei Tomioka ,&nbsp;Chang Dong ,&nbsp;Ao Lin ,&nbsp;Wen-Jie Song","doi":"10.1016/j.heares.2025.109275","DOIUrl":"10.1016/j.heares.2025.109275","url":null,"abstract":"<div><div>Layer 1 (L1) of the neocortex integrates bottom-up and top-down signals. Inputs to L1, however, remain incompletely characterized. L1 of the auditory cortex (ACX) receives ascending inputs from the medial geniculate body (MGB) subdivisions and the surrounding posterior thalamic nuclei (PTN). The precise manner in which these structures innervate L1 is not fully understood. Here we examined the distribution of axon terminals from MGB/PTN subdivisions in L1 of the mouse ACX using virus-based axonal labeling. A bulk injection into the entire MGB and its adjacent PTN (referred to as W) confirmed their projection to upper L1, in addition to other layers. However, we observed multiple vertical axon bundles with irregular inter-bundle intervals in L2 in coronal sections. To identify their origin, we first applied a retrograde tracer to the surface of the ACX and found labeled cell bodies across MGB/PTN subdivisions. The distribution of labeled cells could be dichotomously divided into a dorsomedial (DM) region, primarily encompassing the dorsal and medial nuclei of MGB, and a ventrolateral (VL) region, primarily containing the marginal zone (MZ) of PTN. Sparsely labeled neurons in the caudal part of the ventral MGB (MGv) were also observed. We then injected the virus tracer into the DM region containing the dorsomedial subdivisions of MGB and the dorsomedial MGv (dmMGB), and into the VL region containing the MZ and the ventrolateral MGv, for anterograde labeling of axons. A DM injection resulted in strong, uniform labeling of axons in upper L1, without apparent axon bundles in L2, while a VL injection produced clear axon bundles in L2, as well as labeling in upper L1. The bundle density and inter-bundle interval were not significantly different between the W and VL injection cases, suggesting that the MZ is the primary origin of the axon bundles in L2. Interestingly, axons labeled by VL injections had a higher density at locations where the axon bundles reached upper L1, resulting in a clustered distribution of axons in this layer. Coherence analyses confirmed that axon density in upper L1 varied in phase with that in L2 for the VL injection cases. In tangential sections, axons labeled by W injections in lower L1 appeared to distribute in a square grid-like pattern, with expanded nodes. Quantitative analysis revealed that the axon bundles in coronal sections predominantly corresponded to the grid nodes in the tangential sections. Taken together, our results suggest a strong, uniform distribution of dmMGB axon terminals and a square grid-like distribution of MZ axon terminals in cortical upper L1. These two ascending inputs may exert differential influences on the function of L1 in the ACX.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"462 ","pages":"Article 109275"},"PeriodicalIF":2.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868390","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":"Clonidine mitigates noise-induced hearing loss by regulating TRPC6-mediated calcium influx in cochlear hair cells","authors":"Wenji Zhai ,&nbsp;Xiaojing Kuang ,&nbsp;Jie Wu ,&nbsp;Liheng Li ,&nbsp;Bo Li ,&nbsp;Ruishuang Geng ,&nbsp;Tihua Zheng ,&nbsp;Qingyin Zheng","doi":"10.1016/j.heares.2025.109284","DOIUrl":"10.1016/j.heares.2025.109284","url":null,"abstract":"<div><div>Noise-induced hearing loss (NIHL) is a common auditory disorder driven by calcium overload, oxidative stress, and apoptosis in cochlear sensory hair cells. The transient receptor potential canonical 6 (TRPC6), a nonselective cation channel that can be activated by norepinephrine, is implicated in calcium influx and associated cellular damage. This study explores the protective effects of clonidine, an FDA-approved α2-adrenergic receptor agonist that reduces sympathetic nervous system activity and norepinephrine release, on NIHL in mice. Clonidine treatment significantly preserved hearing thresholds, reduced damage to outer hair cells and ribbon synapses, and suppressed TRPC6 channel activation induced by noise exposure. Mechanistically, clonidine alleviated calcium influx, inhibited the calcium-dependent MLCK-MRLC signaling pathway, and attenuated oxidative stress and apoptosis in cochlear hair cells. Molecular docking analyses demonstrated strong binding between norepinephrine and TRPC6, elucidating the regulatory role of clonidine in calcium signaling. These findings highlight clonidine's potential to prevent NIHL by maintaining intracellular calcium homeostasis and reducing cochlear damage via the modulation of norepinephrine and TRPC6 activity. TRPC6 emerges as a promising therapeutic target for preventing and managing noise-induced auditory dysfunction.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"462 ","pages":"Article 109284"},"PeriodicalIF":2.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863540","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":"Assessing Behavioral and Neural Correlates of Change Detection in Spatialized Acoustic Scenes","authors":"Katarina C. Poole ,&nbsp;Drew Cappotto ,&nbsp;Vincent Martin ,&nbsp;Jakub Sztandera ,&nbsp;Maria Chait ,&nbsp;Lorenzo Picinali ,&nbsp;Martha Shiell","doi":"10.1016/j.heares.2025.109283","DOIUrl":"10.1016/j.heares.2025.109283","url":null,"abstract":"<div><div>The ability to detect changes in complex auditory scenes is crucial for human survival, yet the neural mechanisms underlying this process remain elusive. This study investigates how the presence and location of sound sources impacts active auditory change detection as well as neural correlates of passive change detection. Stimuli were naturalistic temporal envelopes applied to synthesized broadband carriers designed to eliminate semantics and minimize contextual information while preserving naturalistic temporal envelopes and broadband spectra, presented in a spatial loudspeaker array. Behavioral change detection experiments tasked participants with detecting new sources added to spatialized and non-spatialized multi-source auditory scenes. In a passive listening experiment, participants were given a visual decoy task while neural data were collected via electroencephalography (EEG) during exposure to unattended spatialized scenes and added sources.</div><div>Our two behavioral experiments (N = 21 and 21) demonstrated that spatializing sounds facilitated change detection compared to non-spatialized presentation, but that performance declined with increasing number of sound sources and higher hearing thresholds at mid-high frequencies, exclusively in spatialized conditions. Slower reaction times were also observed when changes occurred from above or behind the listener, exacerbated by a higher number of sources. Two EEG experiments (N = 32 and 30), using the same stimuli, showed robust change-evoked responses. However, no significant differences were detected in our analysis as a function of spatial location of the appearing source. These findings provide fresh insights into the mechanisms of spatial auditory change detection, emphasizing the dynamic interplay of spatial cues, change location, and scene complexity.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"462 ","pages":"Article 109283"},"PeriodicalIF":2.5,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874514","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":"Peripheral and central auditory dysfunction induced by intermittent hypoxia via a novel recurrent airway obstruction device in rats","authors":"Yue Wu ,&nbsp;Tao Li ,&nbsp;Dong Shao ,&nbsp;Yiwei Wang ,&nbsp;Boyu Chen ,&nbsp;Yan Yan ,&nbsp;Furong Ma","doi":"10.1016/j.heares.2025.109277","DOIUrl":"10.1016/j.heares.2025.109277","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the effects of intermittent hypoxia (IH) on auditory thresholds, auditory brainstem response (ABR) latency, and neuronal activity in the auditory cortex using a novel recurrent airway obstruction device.</div></div><div><h3>Methods</h3><div>Twenty-four male Sprague–Dawley rats (300–350 g) were randomly assigned to experimental or control groups. A custom 3D-printed mask with one-way valves and a ventilation system was used to induce IH in the experimental group via periodic airflow cessation. The control group wore the same apparatus without hypoxic exposure. Blood oxygen saturation was continuously monitored using a pulse oximeter. A three-dimensional gas dynamics model was constructed to validate the oxygen and carbon dioxide dynamics within the mask. After 3 h of exposure, ABR and the spontaneous firing rate (SFR) of auditory cortical neurons were recorded.</div></div><div><h3>Results</h3><div>The experimental group showed periodic desaturation, with minimum and maximum oxygen saturation values of 80.19 ± 0.34 % and 97.68 ± 0.31 %, respectively. ABR thresholds at 24 and 32 kHz significantly increased to 19.17 ± 1.54 dB and 25.00 ± 1.83 dB (<em>P</em> <em>&lt;</em> <em>0.05</em>). ABR wave III–V latency at 32 kHz was significantly shortened from 2.79 ± 0.17 ms to 2.27 ± 0.16 ms (<em>P</em> <em>&lt;</em> <em>0.05</em>). Additionally, the SFR of auditory cortical neurons increased to 2.67 ± 0.18 Hz in the experimental group versus 1.02 ± 0.11 Hz in controls (<em>P</em> <em>&lt;</em> <em>0.01</em>).</div></div><div><h3>Conclusion</h3><div>Short-term IH induces high-frequency hearing loss, reduces ABR latency, and enhances cortical neuronal excitability, implicating both peripheral and central auditory pathways.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"462 ","pages":"Article 109277"},"PeriodicalIF":2.5,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886896","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":"Sustained Wnt signaling in the mouse inner ear after morphogenesis: In hair cells, supporting cells, and spiral ganglion neurons","authors":"Teppei Noda ,&nbsp;Takahiro Wakizono ,&nbsp;Takahiro Manabe ,&nbsp;Kei Aoyagi ,&nbsp;Marie Kubota ,&nbsp;Tetsuro Yasui ,&nbsp;Takashi Nakagawa ,&nbsp;Kinichi Nakashima ,&nbsp;Chikara Meno","doi":"10.1016/j.heares.2025.109282","DOIUrl":"10.1016/j.heares.2025.109282","url":null,"abstract":"<div><div>The regenerative capacity of inner ear hair cells in mammals varies between the cochlea and the vestibular system. Hair cells in the cochlea lack regenerative ability, whereas those in the vestibular system exhibit limited regenerative potential. However, supporting cells in the cochlea retain proliferative capacity, making them a key focus in auditory regeneration research. Similarly, spiral ganglion neurons actively proliferate until birth but lose this ability within a week postnatally, sharing the regenerative limitations of hair cells. This study investigated the role of the canonical Wnt signaling pathway as a potential regulator of these cells. Wnt signaling plays a crucial role in otic development and inner ear morphogenesis. Using reporter mice, we analyzed the activity of the Wnt canonical pathway in the inner ear at the cellular stages from embryonic to adult stages, assessing fluorescence intensities as an indicator of signaling activity. Our findings demonstrate that Wnt signaling remains active in the vestibular hair cells and in the supporting cells of both the cochlea and vestibule throughout development and into adulthood. In addition, Wnt activity was observed in spiral ganglion neurons up to 7 days after birth, coinciding with their period of proliferative potential. These findings suggest that Wnt signaling is integral to cell proliferation in the inner ear both before and after birth.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"462 ","pages":"Article 109282"},"PeriodicalIF":2.5,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860249","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":"Editorial, Hear Res 2024","authors":"Pascal Barone ,&nbsp;Andrej Kral","doi":"10.1016/j.heares.2025.109281","DOIUrl":"10.1016/j.heares.2025.109281","url":null,"abstract":"","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"461 ","pages":"Article 109281"},"PeriodicalIF":2.5,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900048","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 cortilymph wave: Its relation to the traveling wave, auditory-nerve responses, and low-frequency downward glides","authors":"John J. Guinan Jr","doi":"10.1016/j.heares.2025.109279","DOIUrl":"10.1016/j.heares.2025.109279","url":null,"abstract":"<div><div>In the cochlear base, recent data show that amplification of the traveling wave does <em>not</em> come from outer-hair-cell (OHC) forces acting on the basilar membrane (BM). Instead, traveling wave amplification is hypothesized to come from OHCs producing cyclic cortilymph flow along the organ-of-Corti (OoC) tunnels (the “cortilymph wave”), which changes OoC cross-section area and adds energy to the scala-media-fluid traveling wave. This hypothesis accounts for amplification of cochlear-motion in the base but may not work in the low-frequency apex. One base-to-apex difference is the OHC-membrane resistance-capacitance (RC) low-pass filter. Measurements in live animals found the OHC-RC corner frequency, Fc, was ∼3 kHz. At tone frequencies &gt;&gt;Fc, the RC filter delays the cortilymph wave from the traveling wave by ¼ cycle, which provides the correct timing for OoC-area-change traveling-wave amplification. However, at frequencies &lt;&lt;Fc, the RC-filter delay is shorter, so traveling-wave amplification may be different in the low-frequency cochlear apex. A source of data for understanding low-frequency cochlear mechanics is auditory-nerve (AN) data. AN rate-vs-level functions show two components separated by a phase jump. The frequency relative to the fiber characteristic frequency (CF) where the jump is a phase reversal varies across fibers. This variation is hypothesized to be due to a variable phase relationship of the cortilymph and traveling waves. It is further hypothesized (1) that low-CF AN-tuning-curve “side lobes” have short group delays because they are excited by a cortilymph wave that flows ahead of the traveling wave, and (2) low-CF AN-fiber impulse-response instantaneous-frequency-versus-time profiles (glides) are downward mostly due to a cortilymph wave driven from more basal OHCs. A long downward glide may indicate the presence of a cortilymph wave. Cochlear output is driven by both the traveling wave and the cortilymph wave.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"462 ","pages":"Article 109279"},"PeriodicalIF":2.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850105","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":"Coupling-induced tunability of characteristic frequency, bandwidth and gain of artificial hair cells","authors":"Kalpan Ved ,&nbsp;Hermann Folke Johann Rolf ,&nbsp;Tzvetan Ivanov ,&nbsp;Thomas Meurer ,&nbsp;Martin Ziegler ,&nbsp;Claudia Lenk","doi":"10.1016/j.heares.2025.109260","DOIUrl":"10.1016/j.heares.2025.109260","url":null,"abstract":"<div><div>Drawing inspiration from nature, we develop bio-inspired acoustic sensors with integrated signal processing capabilities to (i) close the performance gap between the human hearing and machine hearing and (ii) test models on biological hearing. Particularly important is thereby the combination of frequency decomposition with nonlinear (compressive) amplification of the sound signals. Here, the question arises, how the frequency resolution of 0.1–0.4%, the large gain and the coverage of the large frequency range of 20 Hz to 20 kHz can be obtained with a modest number of 3000 inner hair cells as transducers without missing tones. To solve this issue, it was hypothesized that the cochlea can be modeled as coupled critical oscillators. We study experimentally and theoretically the effects of coupling critical oscillators using bio-inspired acoustic sensors, which are based-on microelectromechanical system (MEMS) resonators with a high-quality factor and a resonance frequency set by the geometry. Using electronic feedback, these resonators act like critical oscillators tuned near Andronov–Hopf bifurcation point. If output-signal coupling is added, three different bifurcation points are generated. Tuning the system close to one of these bifurcation points leads to a highly tunable behavior and sound pressure dependent sensitivity that is compressive in nature. In this case, the response frequency of the sensor system can be shifted by tuning the control parameter for bifurcation, allowing to cover larger bandwidths with one sensor pair while retaining high quality factors. Furthermore, tuning coupling and feedback strength, bandwidth and gain of each sensor can be adapted as needed. Using these effects, an adaptive filter bank to model the cochlear functionality and adaptation can be build. Since efferent feedback can tune the response of outer hair cells and thus inner hair cells and basilar membrane as well, the question arises if such tuning mechanisms can be observed in the mammalian cochlea as well.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"462 ","pages":"Article 109260"},"PeriodicalIF":2.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839396","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}