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1.
Neural Dev ; 17(1): 6, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524278

RESUMO

BACKGROUND: Fine-tuned cochlear development is essential for hearing. Owing to the difficulty in using early human fetal samples, most of our knowledge regarding cochlear development has been obtained from rodents. However, several inter-species differences in cochlear development between rodents and humans have been reported. To bridge these differences, we investigated early otic development of a non-human primate model animal, the common marmoset (Callithrix jacchus). METHODS: We examined 20 genes involved in early cochlear development and described the critical developmental steps for morphogenesis, which have been reported to vary between rodents and marmosets. RESULTS: The results revealed that several critical genes involved in prosensory epithelium specifications showed higher inter-species differences, suggesting that the molecular process for hair cell lineage acquisition in primates differs considerably from that of rodents. We also observed that the tempo of cochlear development was three times slower in the primate than in rodents. CONCLUSIONS: Our data provide new insights into early cochlear development in primates and humans and imply that the procedures used for manipulating rodent cochlear sensory cells cannot be directly used for the research of primate cells due to the intrinsic inter-species differences in the cell fate determination program.


Assuntos
Callithrix , Cóclea , Animais , Callithrix/genética , Diferenciação Celular , Humanos
2.
J Vis Exp ; (182)2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35532259

RESUMO

The loss of ribbon synapses connecting inner hair cells and afferent auditory nerve fibers is assumed to be one cause of age-related hearing loss. The most common method for detecting the loss of ribbon synapses is immunolabeling because it allows for quantitative sampling from several tonotopic locations in an individual cochlea. However, the structures of interest are buried deep inside the bony cochlea. Gerbils are used as an animal model for age-related hearing loss. Here, routine protocols for fixation, immunolabeling gerbil cochlear whole mounts, confocal imaging, and quantifying ribbon synapse numbers and volumes are described. Furthermore, the particular challenges associated with obtaining good material from valuable aging individuals are highlighted. Gerbils are euthanized and either perfused cardiovascularly, or their tympanic bullae are carefully dissected out of the skull. The cochleae are opened at the apex and base and directly transferred to the fixative. Irrespective of the initial method, the cochleae are postfixed and subsequently decalcified. The tissue is then labeled with primary antibodies against pre- and postsynaptic structures and hair cells. Next, the cochleae are incubated with secondary fluorescence-tagged antibodies that are specific against their respective primary ones. The cochleae of aged gerbils are then treated with an autofluorescence quencher to reduce the typically substantial background fluorescence of older animals' tissues. Finally, cochleae are dissected into 6-11 segments. The entire cochlear length is reconstructed such that specific cochlear locations can be reliably determined between individuals. Confocal image stacks, acquired sequentially, help visualize hair cells and synapses at the chosen locations. The confocal stacks are deconvolved, and the synapses are either counted manually using ImageJ, or more extensive quantification of synaptic structures is carried out with image analysis procedures custom-written in Matlab.


Assuntos
Cóclea , Perda Auditiva , Animais , Gerbillinae , Células Ciliadas Auditivas Internas , Sinapses
3.
Laryngorhinootologie ; 101(5): 428-441, 2022 05.
Artigo em Alemão | MEDLINE | ID: mdl-35500581

RESUMO

Personalized care in the context of cochlear implantation is becoming increasingly important. Choosing the right electrode could improve speech understanding. The measurement of the cochlear length plays an important role: preoperatively, in order to select a suitable electrode length; postoperatively, on the one hand to check the correct electrode position, on the other hand to enable anatomically based fitting of the electrode contacts. Of the various possible localizations of the CDL measurements within the cochlear turns, the one on the organ of Corti (CDLOC) is the most frequently used and clinically most important. In the CDL measurement, a direct and indirect evaluation can be distinguished. There is also the possibility of reconstructing and measuring the CDL in 3D and calculating it mathematically, e.g. using spiral equations. In this context, measurements based on radiological imaging are gaining increasing importance. Therefore, if there is the possibility of performing higher-resolution imaging, this should be strived preoperatively in order to enable the most precise possible procedure and thus a good outcome. Otological planning software can help to create an interface between new findings regarding CDL measurement and higher-resolution imaging for an individualized cochlear implantation.


Assuntos
Implante Coclear , Implantes Cocleares , Cóclea/diagnóstico por imagem , Cóclea/cirurgia , Ducto Coclear/cirurgia , Implante Coclear/métodos , Humanos , Tomografia Computadorizada por Raios X/métodos
4.
Artigo em Chinês | MEDLINE | ID: mdl-35545589

RESUMO

Objective: To study the protective effects of metformin on noise-induced hearing loss (NIHL) and its differential protein omics expression profile. Methods: In January 2021, 39 male Wistar rats were randomly divided into control group, noise exposure group and metformin+noise exposure group, with 13 rats in each group. Rats in the noise exposure group and metformin+noise exposure group were continuously exposed to octave noise with sound pressure level of 120 dB (A) and center frequency of 8 kHz for 4 h. Rats in the metformin+noise exposure group were treated with 200 mg/kg/d metformin 3 d before noise exposure for a total of 7 d. Auditory brainstem response (ABR) was used to test the changes of hearing thresholds before noise exposure and 1, 4, 7 d after noise exposure in the right ear of rats in each group. Tandem mass tag (TMT) quantitative proteomics was used to identify and analyze the differentially expressed protein in the inner ear of rats in each group, and it was verified by immunofluorescence staining with frozen sections. Results: The click-ABR thresholds of right ear in the noise exposure group and metformin+noise exposure group were significantly higher than those in the control group 1, 4, 7 d after noise exposure (P<0.05) . The click-ABR threshold of right ear in the metformin+noise exposure group were significantly lower than that in the noise exposure group (P<0.05) . Compared with the noise exposure group, 1035 up-regulated proteins and 1145 down-regulated proteins were differentially expressed in the metformin+noise exposure group. GO enrichment analysis showed that the significantly differentially expressed proteins were mainly involved in binding, molecular function regulation, signal transduction, and other functions. Enrichment analysis of KEGG pathway revealed that the pathways for significant enrichment of differentially expressed proteins included phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway, focal adhesion, diabetic cardiomyopathy, mitogen, and mitogen-activated protein kinase (MAPK) signaling pathway. Immunofluorescence experiments showed that compared with the noise exposure group, the fluorescence intensity of insulin-like growth factor 1 receptor (IGF1R) in the metformin+noise exposure group was increased, and the fluorescence intensity of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1) was decreased. Conclusion: Noise exposure can lead to an increase in rat hearing threshold, and metformin can improve noise-induced hearing threshold abnormalities through multiple pathways and biological processes.


Assuntos
Orelha Interna , Perda Auditiva Provocada por Ruído , Metformina , Animais , Limiar Auditivo/fisiologia , Cóclea , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Perda Auditiva Provocada por Ruído/metabolismo , Masculino , Metformina/metabolismo , Metformina/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Ratos , Ratos Wistar
5.
PLoS One ; 17(4): e0266077, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35452461

RESUMO

Access to low-frequency acoustic information in cochlear implant patients leads to better speech understanding in noise. Electrocochleography (ECochG) can provide real-time feedback about the health of the cochlea during the insertion process with the potential to reduce insertion trauma. We describe our experiences of using this technique. Data from 47 adult subjects with measurable residual hearing and an Advanced Bionics (Valencia, CA) SlimJ (46) or MidScala (1) electrode array were analyzed. ECochGs were recorded intraoperatively via the implant. The surgeon adjusted the course of the electrode insertion based on drops in the ECochG. The final array position was assessed using postoperative imaging and pure tone thresholds were measured before and after surgery. Three different patterns of ECochG response amplitude were observed: Growth, Fluctuating and Total Loss. Subjects in the growth group showed the smallest postoperative hearing loss. However, the group with fluctuating amplitudes showed no meaningful correlation between the ECochG responses and the postoperative hearing loss, indicating that amplitude alone is insufficient for detecting damage. Considering the phase of the signal additionally to the amplitude and reclassifying the data by both the phase and amplitude of the response into three groups Type I-Type III produced statistically significant correlations between postoperative hearing loss and the grouping based on amplitude and phase respectively. We showed significantly better hearing preservation for Type I (no drop in amplitude) and Type II (drop with a concurrent phase shift), while Type III (drop without concurrent phase shift) had more surgery induced hearing loss. ECochG potentials measured through the implant could provide valuable feedback during the electrode insertion. Both the amplitude and phase of the ECochG response are important to consider. More data needs to be evaluated to better understand the impact of the different signal components to design an automated system to alert the surgeon ahead of damaging the cochlea.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Perda Auditiva , Adulto , Audiometria de Resposta Evocada/métodos , Cóclea/cirurgia , Implante Coclear/métodos , Surdez/cirurgia , Audição , Perda Auditiva/cirurgia , Humanos
6.
J Acoust Soc Am ; 151(4): 2688, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35461519

RESUMO

The best cochlear-neural delay model for designing a chirp that can produce the largest auditory brainstem response (ABR) has not been established. This study comprised two experiments. Experiment I aimed to estimate the delay model by measuring derived-band ABR latencies at different levels. The results demonstrated that, as the level decreased, the delay between the center frequencies of 0.7 and 5.7 kHz increased. The aim of experiment II was to compare ABRs generated by three stimuli: (1) a level-dependent derived-band (DB)-Chirp, designed based on the model in experiment I; (2) a level-dependent level specific (LS)-Chirp from Kristensen and Elberling [(2012). J. Am. Acad. Audiol. 23, 712-721]; and (3) a click. The results demonstrated that the DB-Chirp produced significantly larger wave V than the LS-Chirp at 45 dB normal hearing level (nHL); however, no differences were observed at other levels. The wave I generated by the DB-Chirp and LS-Chirp were significantly larger than those evoked by the click at 45 and 60 dB nHL and at 30 and 45 dB nHL, respectively; however, at all levels, no differences between these two chirps were observed. The DB-Chirp may be a valuable stimulus for producing ABRs for clinical applications such as assessing cochlear synaptopathy and estimating hearing sensitivity.


Assuntos
Potenciais Evocados Auditivos do Tronco Encefálico , Audição , Estimulação Acústica/métodos , Limiar Auditivo/fisiologia , Cóclea/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Audição/fisiologia , Testes Auditivos
7.
Biomed Res Int ; 2022: 9079903, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35411307

RESUMO

Active transcutaneous bone conduction (BC) devices offer the benefit of improved power output compared to passive transcutaneous devices and remove the risk of skin infections that are more common in traditional percutaneous BC devices. Despite these advantages, more research is needed on implant location, device coupling, and their influence on device performance. This study is aimed at quantifying the extent to which certain parameters affect device output when using the Osia® system actuator. Parameters under study are (1) implant location, (2) comparison with the actuator of a state-of-the-art BC device, (3) bone undergrowth simulation, and (4) skull fixation. Five human cadaveric heads were implanted with the actuator at three different implant locations: (1) recommended, (2) posterior Osia® positions, and (3) standard Baha® position. At each location, the cochlear promontory velocity and the intracochlear pressure difference were measured. A percutaneous bone conduction actuator was used as a reference for the obtained measurements. Stimulation levels corresponded to a hearing level of 60 dB HL for frequencies between 250 and 6000 Hz. In addition, bone cement was used as a simulation for reactive bone growth. Results obtained in four heads indicate an improved power transmission of the transcutaneous actuator when implanted at the recommended position compared to the actuator of the percutaneous device on its respective recommended location when stimulating at an identical force level. A correlation was found between the promontory vibration and the actuator position, indicating that the same level of stimulation leads to higher promontory vibrations when the device is implanted closer to the ear canal. This is mainly reflected at frequencies higher than 1 kHz, where an increase was observed in both measurement modalities. At lower frequencies (<1 kHz), the power transmission is less influenced by the implant position and differences between the acquired responses are limited. In addition, when no rigid coupling to the skull is provided, power transfer losses of up to 30 dB can be expected.


Assuntos
Condução Óssea , Auxiliares de Audição , Condução Óssea/fisiologia , Cóclea/fisiologia , Humanos , Crânio , Vibração
8.
J Int Adv Otol ; 18(2): 96-99, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35418355

RESUMO

BACKGROUND: The aim of this study is to analyze the effect of collagen viscoelastoplasticity on the bulge displacement of Reissner's membrane that is observed in endolymphatic hydrops and Meniere's disease. METHODS: Viscoelastoplastic load-deformation characteristics for Reissner's membrane were based on a reported collagen polymer model of the cochleo-saccular membranes. The projected bulge displacements of Reissner's model membrane at key distention points were quantified trigonometrically and plotted graphically. RESULTS: Initial deformation is characterized by a membrane laxity with substantial stretch at low tension with projected bulge displacement of Reissner's membrane approaching 30%. Intermediate deformation is characterized by a linear membrane stiffness with projected bulge displacement of Reissner's membrane in the range of 30-40%. Terminal deformation is characterized by reduced stiffness with a disproportionate increase in membrane stretch with projected bulge displacement of Reissner's membrane reaching a critical value of 50%, indicating a hemi-circular profile with imminent risk of rupture. CONCLUSION: This collagen model of membrane viscoelastoplasticity demonstrates that at low pressure significant degrees of bulge displacement up to 30% can occur that may be reversible. The narrower 30-40% range of membrane displacement is one of the increasing deformity but without risk of rupture. Greater displacements approaching 50% indicate that the membrane is reaching a critical hemi-circular configuration with impending rupture.


Assuntos
Hidropisia Endolinfática , Doença de Meniere , Cóclea , Colágeno , Humanos
9.
J Int Adv Otol ; 18(2): 118-124, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35418359

RESUMO

BACKGROUND: To investigate the possible protective activity of oleuropein compound on noise-induced hearing loss in rats. METHODS: Twenty-eight adult male albino rats were divided into 4 groups. Control normal saline (n=7) group was kept noise-free. Control oleuropein group (n=7) group was kept noise-free and was administered with 50 mg/kg/day oleuropein. The experimental normal saline (n=7) group was subjected to noise. The experimental oleuropein (n=7) group was subjected to noise and was administered with 50 mg/kg/day oleuropein. The experimental groups were subjected to 4 kHz octave noise with a frequency of 120 dB Sound Pressure Level (SPL) for 4 hours. Hearing level measurements were performed with auditory brainstem response and distortion-product otoacoustic emission tests before and after the 1st, 7th, and 10th day of the noise exposure. On the 10th day, rats were sacrificed. The temporal bones of the rats were removed and the cochlea and spiral ganglion cells were evaluated using hematoxylin-eosin staining under light microscopy. RESULTS: Better hearing thresholds were achieved in the experimental oleuropein group compared to the experimental normal saline group at 8 kHz, 12 kHz, 16 kHz, and 32 kHz frequencies (P < .05). Although no statistically significant difference was found between the groups, in the experimental normal saline group, the percentage of damaged spiral ganglion cells was higher than the experimental oleuropein group. CONCLUSION: Our findings suggest that oleuropein may have a partial protective effect against noise-related hearing loss. However, further research with higher doses is needed to justify this protective effect.


Assuntos
Perda Auditiva Provocada por Ruído , Animais , Limiar Auditivo/fisiologia , Cóclea , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Perda Auditiva Provocada por Ruído/tratamento farmacológico , Perda Auditiva Provocada por Ruído/prevenção & controle , Glucosídeos Iridoides , Masculino , Emissões Otoacústicas Espontâneas/fisiologia , Ratos , Solução Salina/farmacologia
10.
Cell Rep ; 39(2): 110665, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35417713

RESUMO

Age-related hearing loss (ARHL) negatively impacts quality of life in the elderly population. The prevalent cause of ARHL is loss of mechanosensitive cochlear hair cells (HCs). The molecular and cellular mechanisms of HC degeneration remain poorly understood. Using RNA-seq transcriptomic analyses of inner and outer HCs isolated from young and aged mice, we show that HC aging is associated with changes in key molecular processes, including transcription, DNA damage, autophagy, and oxidative stress, as well as genes related to HC specialization. At the cellular level, HC aging is characterized by loss of stereocilia, shrinkage of HC soma, and reduction in outer HC mechanical properties, suggesting that functional decline in mechanotransduction and cochlear amplification precedes HC loss and contributes to ARHL. Our study reveals molecular and cytological profiles of aging HCs and identifies genes such as Sod1, Sirt6, Jund, and Cbx3 as biomarkers and potential therapeutic targets for ameliorating ARHL.


Assuntos
Envelhecimento , Células Ciliadas Auditivas Externas , Idoso , Envelhecimento/fisiologia , Animais , Proteínas Cromossômicas não Histona , Cóclea , Humanos , Mecanotransdução Celular , Camundongos , Qualidade de Vida
11.
Cell Death Dis ; 13(4): 343, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35418568

RESUMO

Age-related hearing loss (AHL) is the most common sensory disorder amongst the elderly population. Although the degeneration of spiral ganglion neurons (SGNs) and hair cells (HCs) is considered to play a critical role in AHL, the mechanism has not been fully outlined. The repressor element 1-silencing transcription factor (REST) has recently been associated with mediating cell death in neurodegenerative diseases. However, whether REST induces degeneration of cochlear HCs and SGNs to contribute to AHL remains unknown. Here, we report that REST expression was decreased in HCs and SGNs in AHL mice. Conditional deletion of Rest in HCs and SGNs of 2-month-old mice resulted in hearing loss accompanied by the upregulation of p53, TNFR1(tumor necrosis factor receptor-1), and cleaved caspase-3. The p53 inhibitor pifithrin-α significantly attenuated SGN and HC damage and rescued hearing impairment in Rest cKO mice. Furthermore, downregulation of REST by H2O2 treatment induced apoptosis in the House Ear Institute Organ of Corti 1 cell, through the upregulation of p53. In contrast, overexpression of REST reversed the changes in p53 expression. In addition, REST was further shown to bind directly to the p53 promoter site, thereby inhibiting the effect of p53. Finally, in aged mice, the p53 inhibitor significantly reduced loss of HCs and SGNs, and subsequently improved hearing. In summary, our findings indicate that REST has a protective role in AHL, and that its deficiency upregulates p53 and induces cochlear cell apoptosis, which that leads to deafness.


Assuntos
Perda Auditiva , Proteína Supressora de Tumor p53 , Idoso , Animais , Apoptose , Cóclea/patologia , Regulação para Baixo , Perda Auditiva/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Camundongos , Gânglio Espiral da Cóclea , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
12.
J Assoc Res Otolaryngol ; 23(3): 379-389, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35378622

RESUMO

Integration of acoustic information over time is essential for processing complex stimuli, such as speech, due to its continuous variability along the time domain. In both humans and animals, perception of acoustic stimuli is a function of both stimulus intensity and duration. For brief acoustic stimuli, as duration increases, thresholds decrease by approximately 3 dB for every doubling in duration until stimulus duration reaches 500 ms, a phenomenon known as temporal integration. Although hearing loss and damage to outer hair cells (OHC) have been shown to alter temporal integration in some studies, the role of cochlear inner hair cells (IHC) on temporal integration is unknown. Because IHC transmit nearly all acoustic information to the central auditory system and are believed to code both intensity and timing information, these sensory cells likely play a critical role in temporal integration. To test the hypothesis that selective IHC loss degrades the temporal integration function, behaviorally trained chinchillas were treated with carboplatin, a drug known to selectively destroy IHC with little to no effect on OHC in this species. Pure-tone thresholds were assessed across frequencies (1, 2, 4, 8, 12 kHz) as a function of signal duration (500, 100, 50, 10, and 5 ms). Baseline testing showed a significant effect of duration on thresholds. Threshold decreased as a function of increasing duration, as expected. Carboplatin treatment (75 mg/kg) produced a moderate to severe loss of IHC (45-85%) with little-to-no loss of OHC. Contrary to our hypothesis, post-carboplatin temporal integration thresholds showed no significant differences from baseline regardless of stimulus duration or frequency. These data suggest that few IHC are necessary for temporal integration of simple stimuli. Temporal integration may be sensitive to loss of OHC and loss of cochlear non-linearities but does not appear to be sensitive to selective IHC loss.


Assuntos
Células Ciliadas Auditivas Internas , Células Ciliadas Auditivas Externas , Animais , Limiar Auditivo , Carboplatina/toxicidade , Chinchila , Cóclea
13.
Development ; 149(8)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35420675

RESUMO

The avian hearing organ is the basilar papilla that, in sharp contrast to the mammalian cochlea, can regenerate sensory hair cells and thereby recover from deafness within weeks. The mechanisms that trigger, sustain and terminate the regenerative response in vivo are largely unknown. Here, we profile the changes in gene expression in the chicken basilar papilla after aminoglycoside antibiotic-induced hair cell loss using RNA-sequencing. We identified changes in gene expression of a group of immune-related genes and confirmed with single-cell RNA-sequencing that these changes occur in supporting cells. In situ hybridization was used to further validate these findings. We determined that the JAK/STAT signaling pathway is essential for upregulation of the damage-response genes in supporting cells during the second day after induction of hair cell loss. Four days after ototoxic damage, we identified newly regenerated, nascent auditory hair cells that express genes linked to termination of the JAK/STAT signaling response. The robust, transient expression of immune-related genes in supporting cells suggests a potential functional involvement of JAK/STAT signaling in sensory hair cell regeneration.


Assuntos
Galinhas , Células Ciliadas Auditivas , Animais , Antibacterianos , Cóclea , Células Ciliadas Auditivas/metabolismo , Mamíferos , RNA/metabolismo
14.
Stem Cell Res ; 61: 102758, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35364395

RESUMO

Hearing loss is one of the most common sensory disorders. TMEM43 is expressed in cochlear glia-like supporting cells (GLSs) and is known to be associated with late-onset auditory neuropathy spectrum disorder (ANSD) and progressive hearing loss. Here, we describe the derivation of an induced pluripotent stem cell (iPSC) line from a patient lymphoblastoid cell line (LCL) carrying a single heterozygous nonsense variant (p.Arg372Ter (c.1114C > T)) in TMEM43 that leads to a truncated protein lacking the 4th transmembrane domain. This cell line can serve as a tool for disease modelling and development of therapeutic approaches to restore inner ear function.


Assuntos
Perda Auditiva Central , Células-Tronco Pluripotentes Induzidas , Linhagem Celular , Cóclea , Perda Auditiva Central/genética , Perda Auditiva Central/terapia , Humanos , Proteínas de Membrana
15.
Cells ; 11(7)2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-35406660

RESUMO

Our senses define our view of the world. They allow us to adapt to environmental stimuli and are essential for communication and social behaviour. For most humans, seeing and hearing are central senses for their daily life. Our eyes and ears respond to an extraordinary broad range of stimuli covering about 12 log units of light intensity or acoustic power, respectively. The cellular basis is represented by sensory cells (photoreceptors in the retina and inner hair cells in the cochlea) that convert sensory inputs into electrical signals. Photoreceptors and inner hair cells have developed a specific pre-synaptic structure, termed synaptic ribbon, that is decorated with numerous vesicles filled with the excitatory neurotransmitter glutamate. At these ribbon synapses, glutamatergic signal transduction is guided by distinct sets of metabotropic glutamate receptors (mGluRs). MGluRs belong to group II and III of the receptor classification can inhibit neuronal activity, thus protecting neurons from overstimulation and subsequent degeneration. Consequently, dysfunction of mGluRs is associated with vision and hearing disorders. In this review, we introduce the principle characteristics of ribbon synapses and describe group II and III mGluRs in these fascinating structures in the retina and cochlea.


Assuntos
Receptores de Glutamato Metabotrópico , Cóclea , Células Ciliadas Auditivas Internas , Humanos , Retina , Sinapses/fisiologia
16.
Signal Transduct Target Ther ; 7(1): 109, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35449181

RESUMO

The cochlea consists of multiple types of cells, including hair cells, supporting cells and spiral ganglion neurons, and is responsible for converting mechanical forces into electric signals that enable hearing. Genetic and environmental factors can result in dysfunctions of cochlear and auditory systems. In recent years, gene therapy has emerged as a promising treatment in animal deafness models. One major challenge of the gene therapy for deafness is to effectively deliver genes to specific cells of cochleae. Here, we screened and identified an AAV-ie mutant, AAV-ie-K558R, that transduces hair cells and supporting cells in the cochleae of neonatal mice with high efficiency. AAV-ie-K558R is a safe vector with no obvious deficits in the hearing system. We found that AAV-ie-K558R can partially restore the hearing loss in Prestin KO mice and, importantly, deliver Atoh1 into cochlear supporting cells to generate hair cell-like cells. Our results demonstrate the clinical potential of AAV-ie-K558R for treating the hearing loss caused by hair cell death.


Assuntos
Surdez , Perda Auditiva , Animais , Cóclea/metabolismo , Surdez/metabolismo , Surdez/terapia , Terapia Genética , Células Ciliadas Auditivas/metabolismo , Perda Auditiva/genética , Perda Auditiva/metabolismo , Perda Auditiva/terapia , Camundongos
17.
J Acoust Soc Am ; 151(4): 2802, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35461487

RESUMO

Accumulating evidence suggests that cochlear deafferentation may contribute to suprathreshold deficits observed with or without elevated hearing thresholds, and can lead to accelerated age-related hearing loss. Currently there are no clinical diagnostic tools to detect human cochlear deafferentation in vivo. Preclinical studies using a combination of electrophysiological and post-mortem histological methods clearly demonstrate cochlear deafferentation including myelination loss, mitochondrial damages in spiral ganglion neurons (SGNs), and synaptic loss between inner hair cells and SGNs. Since clinical diagnosis of human cochlear deafferentation cannot include post-mortem histological quantification, various attempts based on functional measurements have been made to detect cochlear deafferentation. So far, those efforts have led to inconclusive results. Two major obstacles to the development of in vivo clinical diagnostics include a lack of standardized methods to validate new approaches and characterize the normative range of repeated measurements. In this overview, we examine strategies from previous studies to detect cochlear deafferentation from electrocochleography and auditory brainstem responses. We then summarize possible approaches to improve these non-invasive functional methods for detecting cochlear deafferentation with a focus on cochlear synaptopathy. We identify conceptual approaches that should be tested to associate unique electrophysiological features with cochlear deafferentation.


Assuntos
Audiometria de Resposta Evocada , Potenciais Evocados Auditivos do Tronco Encefálico , Limiar Auditivo/fisiologia , Cóclea , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Audição , Humanos , Gânglio Espiral da Cóclea
18.
J Acoust Soc Am ; 151(4): 2391, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35461508

RESUMO

Distortion product otoacoustic emissions (DPOAEs) offer an outcome measure to consider for clinical detection and monitoring outer hair cell dysfunction as a result of noise exposure. This investigation detailed DPOAE characteristics and behavioral hearing thresholds up to 20 kHz to identify promising metrics for early detection of cochlear dysfunction. In a sample of normal-hearing individuals with and without self-reported noise exposure, the DPOAE and hearing threshold measures, as assessed by two questions, were examined. The effects on various auditory measures in individuals aged 10-65 years old with clinically normal/near-normal hearing through 4 kHz were evaluated. Individuals reporting occupational noise exposures (n = 84) and recreational noise exposures (n = 46) were compared to age-matched nonexposed individuals. The hearing thresholds and DPOAE level, fine structure, and component characteristics for the full frequency bandwidth were examined. The data suggest that the DPOAE levels measured using a range of stimulus levels hold clinical utility while fine structure characteristics offer limited use. Under carefully calibrated conditions, the extension to frequencies beyond 8 kHz in combination with various stimulus levels holds clinical utility. Moreover, this work supports the potential utility of the distortion product place component level for revealing differences in cochlear function due to self-reported, casual noise exposure that are not observable in behavioral hearing thresholds.


Assuntos
Testes Auditivos , Emissões Otoacústicas Espontâneas , Adolescente , Adulto , Idoso , Limiar Auditivo , Criança , Cóclea , Audição , Humanos , Pessoa de Meia-Idade , Autorrelato , Adulto Jovem
19.
Artigo em Chinês | MEDLINE | ID: mdl-35483686

RESUMO

Objective:To analyze the objective test results of the pure-tone audiogram (PTA), extended high-frequency audiometry (EHFA), distortion product otoacoustic emission (DPOAE), auditory brainstem response(ABR), and electrocochleogram (ECochG) in patients with unilateral acute tinnitus, summarize their characteristics and explore their clinical application value in hidden hearing loss. Methods:PTA, DPOAE, ABR, and ECochG tests were performed in 33 patients with unilateral acute tinnitus as the chief complaint. The detection rate and response amplitude of each DPOAE frequency, incubation period, and interval of ABR waves and -SP/AP in ECochG were analyzed. Results:①The thresholds of PTA at 0.25-8 kHz in both ears were in the normal range (P>0.05), and the thresholds of PTA at 9-16 kHz in affected ears were higher than those in healthy ears (P<0.001); ②There was statistical significance in the detection rate and response amplitude of DPOAE at 3, 4, 6, 8 kHz between ears (P<0.05); ③The incubation period of ABR Ⅰ wave in affected ears was (1.55±0.17) ms, that in the healthy ear was (1.50±0.14) ms, among them, the incubation period of ABR Ⅰ wave in the affected ear was longer than that in the healthy ear, and the difference was statistically significant (P<0.05); ④In ECochG, there was no significant difference in -SP amplitude between ears (P>0.05), but there was a significant difference in AP amplitude and -SP/AP amplitude between ears (P<0.05). Conclusion:EHFA, DPOAE, ABR, and ECochG have clinical significance in evaluating cochlear function in tinnitus patients.


Assuntos
Zumbido , Audiometria de Tons Puros , Cóclea , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Humanos , Emissões Otoacústicas Espontâneas/fisiologia , Zumbido/diagnóstico
20.
J Acoust Soc Am ; 151(3): 1875, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35364913

RESUMO

In response to an external stimulus, the cochlea emits sounds, called stimulus frequency otoacoustic emissions (SFOAEs), at the stimulus frequency. In this article, a three-dimensional computational model of the gerbil cochlea is used to simulate SFOAEs and clarify their generation mechanisms and characteristics. This model includes electromechanical feedback from outer hair cells (OHCs) and cochlear roughness due to spatially random inhomogeneities in the OHC properties. As in the experiments, SFOAE simulations are characterized by a quasiperiodic fine structure and a fast varying phase. Increasing the sound pressure level broadens the peaks and decreases the phase-gradient delay of SFOAEs. A state-space formulation of the model provides a theoretical framework to analyze the link between the fine structure and global modes of the cochlea, which arise as a result of standing wave resonances. The SFOAE fine structure peaks correspond to weakly damped resonant modes because they are observed at the frequencies of nearly unstable modes of the model. Variations of the model parameters that affect the reflection mechanism show that the magnitude and sharpness of the tuning of these peaks are correlated with the modal damping ratio of the nearly unstable modes. The analysis of the model predictions demonstrates that SFOAEs originate from the peak of the traveling wave.


Assuntos
Cóclea , Emissões Otoacústicas Espontâneas , Cóclea/fisiologia , Células Ciliadas Auditivas Externas , Emissões Otoacústicas Espontâneas/fisiologia , Som
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