scholarly journals Differences in Calcium Clearance at Inner Hair Cell Active Zones May Underlie the Difference in Susceptibility to Noise-Induced Cochlea Synaptopathy of C57BL/6J and CBA/CaJ Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Hongchao Liu ◽  
Hu Peng ◽  
Longhao Wang ◽  
Pengcheng Xu ◽  
Zhaoyan Wang ◽  
...  
Keyword(s):  
Hair Cell ◽  
Clearance Rate ◽  
Noise Exposure ◽  
Auditory Brainstem ◽  
Response Threshold ◽  
Inner Hair Cell ◽  
Cba Mice ◽  
Calcium Clearance ◽  
Brainstem Response ◽  
Susceptibility To Noise

Noise exposure of a short period at a moderate level can produce permanent cochlear synaptopathy without seeing lasting changes in audiometric threshold. However, due to the species differences in inner hair cell (IHC) calcium current that we have recently discovered, the susceptibility to noise exposure may vary, thereby impact outcomes of noise exposure. In this study, we investigate the consequences of noise exposure in the two commonly used animal models in hearing research, CBA/CaJ (CBA) and C57BL/6J (B6) mice, focusing on the functional changes of cochlear IHCs. In the CBA mice, moderate noise exposure resulted in a typical fully recovered audiometric threshold but a reduced wave I amplitude of auditory brainstem responses. In contrast, both auditory brainstem response threshold and wave I amplitude fully recovered in B6 mice at 2 weeks after noise exposure. Confocal microscopy observations found that ribbon synapses of IHCs recovered in B6 mice but not in CBA mice. To further characterize the molecular mechanism underlying these different phenotypes in synaptopathy, we compared the ratio of Bax/Bcl-2 with the expression of cytochrome-C and found increased activity in CBA mice after noise exposure. Under whole-cell patch clamped IHCs, we acquired two-photon calcium imaging around the active zone to evaluate the Ca2+ clearance rate and found that CBA mice have a slower calcium clearance rate. Our results indicated that excessive accumulation of calcium due to acoustic overexposure and slow clearance around the presynaptic ribbon might lead to disruption of calcium homeostasis, followed by mitochondrial dysfunction of IHCs that cause susceptibility of noise-induced cochlear synaptopathy in CBA mice.

scholarly journals Auditory Brainstem Response Altered in Humans With Noise Exposure Despite Normal Outer Hair Cell Function

2017 ◽  
Vol 38 (1) ◽  
pp. e1-e12 ◽  
Author(s):  
Naomi F. Bramhall ◽  
Dawn Konrad-Martin ◽  
Garnett P. McMillan ◽  
Susan E. Griest
Keyword(s):  
Hair Cell ◽  
Auditory Brainstem Response ◽  
Noise Exposure ◽  
Outer Hair Cell ◽  
Cell Function ◽  
Auditory Brainstem ◽  
Brainstem Response

scholarly journals Cochlear NMDA Receptors as a Therapeutic Target of Noise-Induced Tinnitus

2015 ◽  
Vol 35 (5) ◽  
pp. 1905-1923 ◽  
Author(s):  
Dan Bing ◽  
Sze Chim Lee ◽  
Dario Campanelli ◽  
Hao Xiong ◽  
Masahiro Matsumoto ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Auditory Nerve ◽  
Noise Exposure ◽  
Round Window ◽  
Receptor Activation ◽  
Auditory Brainstem ◽  
Nmda Receptor Antagonist ◽  
Inner Hair Cell ◽  
Ribbon Synapses ◽  
Brainstem Response

Background: Accumulating evidence suggests that tinnitus may occur despite normal auditory sensitivity, probably linked to partial degeneration of the cochlear nerve and damage of the inner hair cell (IHC) synapse. Damage to the IHC synapses and deafferentation may occur even after moderate noise exposure. For both salicylate- and noise-induced tinnitus, aberrant N-methyl-d-aspartate (NMDA) receptor activation and related auditory nerve excitation have been suggested as origin of cochlear tinnitus. Accordingly, NMDA receptor inhibition has been proposed as a pharmacologic approach for treatment of synaptopathic tinnitus. Methods: Round-window application of the NMDA receptor antagonist AM-101 (Esketamine hydrochloride gel; Auris Medical AG, Basel, Switzerland) was tested in an animal model of tinnitus induced by acute traumatic noise. The study included the quantification of IHC ribbon synapses as a correlate for deafferentation as well as the measurement of the auditory brainstem response (ABR) to close-threshold sensation level stimuli as an indication of sound-induced auditory nerve activity. Results: We have shown that AM-101 reduced the trauma-induced loss of IHC ribbons and counteracted the decline of ABR wave I amplitude generated in the cochlea/auditory nerve. Conclusion: Local round-window application of AM-101 may be a promising therapeutic intervention for the treatment of synaptopathic tinnitus.

scholarly journals An antibody to RGMa promotes regeneration of cochlear synapses after noise exposure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jerome Nevoux ◽  
Mihaela Alexandru ◽  
Thomas Bellocq ◽  
Lei Tanaka ◽  
Yushi Hayashi ◽  
...  
Keyword(s):  
Hair Cells ◽  
Noise Exposure ◽  
Auditory Brainstem ◽  
Afferent Input ◽  
Nerve Fibers ◽  
Auditory Neuropathy ◽  
Axonal Guidance ◽  
Inner Hair Cell ◽  
Inner Hair Cells ◽  
Brainstem Response

AbstractAuditory neuropathy is caused by the loss of afferent input to the brainstem via the components of the neural pathway comprising inner hair cells and the first order neurons of the spiral ganglion. Recent work has identified the synapse between cochlear primary afferent neurons and sensory hair cells as a particularly vulnerable component of this pathway. Loss of these synapses due to noise exposure or aging results in the pathology identified as hidden hearing loss, an initial stage of cochlear dysfunction that goes undetected in standard hearing tests. We show here that repulsive axonal guidance molecule a (RGMa) acts to prevent regrowth and synaptogenesis of peripheral auditory nerve fibers with inner hair cells. Treatment of noise-exposed animals with an anti-RGMa blocking antibody regenerated inner hair cell synapses and resulted in recovery of wave-I amplitude of the auditory brainstem response, indicating effective reversal of synaptopathy.

scholarly journals Acoustic Trauma Changes the Parvalbumin-Positive Neurons in Rat Auditory Cortex

2018 ◽  
Vol 2018 ◽  
pp. 1-7
Author(s):  
Congli Liu ◽  
Tao Xu ◽  
Xiaopeng Liu ◽  
Yina Huang ◽  
Haitao Wang ◽  
...  
Keyword(s):  
Auditory Cortex ◽  
Noise Exposure ◽  
Stable State ◽  
Auditory Brainstem ◽  
Acoustic Trauma ◽  
Cortical Inhibition ◽  
Response Threshold ◽  
Compensatory Mechanism ◽  
Central System ◽  
Brainstem Response

Acoustic trauma is being reported to damage the auditory periphery and central system, and the compromised cortical inhibition is involved in auditory disorders, such as hyperacusis and tinnitus. Parvalbumin-containing neurons (PV neurons), a subset of GABAergic neurons, greatly shape and synchronize neural network activities. However, the change of PV neurons following acoustic trauma remains to be elucidated. The present study investigated how auditory cortical PV neurons change following unilateral 1 hour noise exposure (left ear, one octave band noise centered at 16 kHz, 116 dB SPL). Noise exposure elevated the auditory brainstem response threshold of the exposed ear when examined 7 days later. More detectable PV neurons were observed in both sides of the auditory cortex of noise-exposed rats when compared to control. The detectable PV neurons of the left auditory cortex (ipsilateral to the exposed ear) to noise exposure outnumbered those of the right auditory cortex (contralateral to the exposed ear). Quantification of Western blotted bands revealed higher expression level of PV protein in the left cortex. These findings of more active PV neurons in noise-exposed rats suggested that a compensatory mechanism might be initiated to maintain a stable state of the brain.

Protective effects of brain-derived neurotrophic factor on the noise-damaged cochlear spiral ganglion

2010 ◽  
Vol 125 (5) ◽  
pp. 449-454 ◽  
Author(s):  
S-Q Zhai ◽  
W Guo ◽  
Y-Y Hu ◽  
N Yu ◽  
Q Chen ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Auditory Brainstem Response ◽  
Noise Exposure ◽  
Recombinant Adenovirus ◽  
Spiral Ganglion ◽  
Brain Derived Neurotrophic Factor ◽  
Auditory Brainstem ◽  
Response Threshold ◽  
Protective Effects ◽  
Brainstem Response

AbstractObjective:To explore the protective effects of brain-derived neurotrophic factor on the noise-damaged cochlear spiral ganglion.Methods:Recombinant adenovirus brain-derived neurotrophic factor vector, recombinant adenovirus LacZ and artificial perilymph were prepared. Guinea pigs with audiometric auditory brainstem response thresholds of more than 75 dB SPL, measured seven days after four hours of noise exposure at 135 dB SPL, were divided into three groups. Adenovirus brain-derived neurotrophic factor vector, adenovirus LacZ and perilymph were infused into the cochleae of the three groups, variously. Eight weeks later, the cochleae were stained immunohistochemically and the spiral ganglion cells counted.Results:The auditory brainstem response threshold recorded before and seven days after noise exposure did not differ significantly between the three groups. However, eight weeks after cochlear perfusion, the group receiving brain-derived neurotrophic factor had a significantly decreased auditory brainstem response threshold and increased spiral ganglion cell count, compared with the adenovirus LacZ and perilymph groups.Conclusion:When administered via cochlear infusion following noise damage, brain-derived neurotrophic factor appears to improve the auditory threshold, and to have a protective effect on the spiral ganglion cells.

scholarly journals Dose-Dependent Pattern of Cochlear Synaptic Degeneration in C57BL/6J Mice Induced by Repeated Noise Exposure

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Minfei Qian ◽  
Qixuan Wang ◽  
Zhongying Wang ◽  
Qingping Ma ◽  
Xueling Wang ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Noise Exposure ◽  
Moderate Intensity ◽  
Intensity Noise ◽  
Inner Hair Cell ◽  
Ribbon Synapses ◽  
Synaptic Degeneration ◽  
Brainstem Response ◽  
Dose Dependent

It is widely accepted that even a single acute noise exposure at moderate intensity that induces temporary threshold shift (TTS) can result in permanent loss of ribbon synapses between inner hair cells and afferents. However, effects of repeated or chronic noise exposures on the cochlear synapses especially medial olivocochlear (MOC) efferent synapses remain elusive. Based on a weeklong repeated exposure model of bandwidth noise over 2-20 kHz for 2 hours at seven intensities (88 to 106 dB SPL with 3 dB increment per gradient) on C57BL/6J mice, we attempted to explore the dose-response mechanism of prolonged noise-induced audiological dysfunction and cochlear synaptic degeneration. In our results, mice repeatedly exposed to relatively low-intensity noise (88, 91, and 94 dB SPL) showed few changes on auditory brainstem response (ABR), ribbon synapses, or MOC efferent synapses. Notably, repeated moderate-intensity noise exposures (97 and 100 dB SPL) not only caused hearing threshold shifts and the inner hair cell ribbon synaptopathy but also impaired MOC efferent synapses, which might contribute to complex patterns of damages on cochlear function and morphology. However, repeated high-intensity (103 and 106 dB SPL) noise exposures induced PTSs mainly accompanied by damages on cochlear amplifier function of outer hair cells and the inner hair cell ribbon synaptopathy, rather than the MOC efferent synaptic degeneration. Moreover, we observed a frequency-dependent vulnerability of the repeated acoustic trauma-induced cochlear synaptic degeneration. This study provides a sight into the hypothesis that noise-induced cochlear synaptic degeneration involves both afferent (ribbon synapses) and efferent (MOC terminals) pathology. The pattern of dose-dependent pathological changes induced by repeated noise exposure at various intensities provides a possible explanation for the complicated cochlear synaptic degeneration in humans. The underlying mechanisms remain to be studied in the future.

scholarly journals SMPX Deficiency Causes Stereocilia Degeneration and Progressive Hearing Loss in CBA/CaJ Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Hailong Tu ◽  
Aizhen Zhang ◽  
Xiaolong Fu ◽  
Shiqi Xu ◽  
Xiaohui Bai ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Noise Exposure ◽  
Muscle Protein ◽  
Auditory Brainstem ◽  
Null Mouse ◽  
Suitable Model ◽  
Human Beings ◽  
Progressive Hearing Loss ◽  
Brainstem Response

The small muscle protein, x-linked (SMPX) encodes a small protein containing 88 amino acids. Malfunction of this protein can cause a sex-linked non-syndromic hearing loss, named X-linked deafness 4 (DFNX4). Herein, we reported a point mutation and a frameshift mutation in two Chinese families who developed gradual hearing loss with age. To explore the impaired sites in the hearing system and the mechanism of DFNX4, we established and validated an Smpx null mouse model using CRISPR-Cas9. By analyzing auditory brainstem response (ABR), male Smpx null mice showed a progressive hearing loss starting from high frequency at the 3rd month. Hearing loss in female mice was milder and occurred later compared to male mice, which was very similar to human beings. Through morphological analyses of mice cochleas, we found the hair cell bundles progressively degenerated from the shortest row. Cellular edema occurred at the end phase of stereocilia degeneration, followed by cell death. By transfecting exogenous fluorescent Smpx into living hair cells, Smpx was observed to be expressed in stereocilia. Through noise exposure, it was shown that Smpx might participate in maintaining hair cell bundles. This Smpx knock-out mouse might be used as a suitable model to explore the pathology of DFNX4.

scholarly journals Tinnitus and Auditory Perception After a History of Noise Exposure: Relationship to Auditory Brainstem Response Measures

2017 ◽  
Author(s):  
Naomi Bramhall
Keyword(s):  
Speech Perception ◽  
Confidence Interval ◽  
Hair Cell ◽  
Auditory Nerve ◽  
Auditory Brainstem Response ◽  
Auditory Perception ◽  
Noise Exposure ◽  
Auditory Brainstem ◽  
Distortion Product ◽  
Brainstem Response

ObjectivesDetermine whether auditory brainstem response (ABR) wave I amplitude is associated with measures of auditory perception in young people with normal distortion product otoacoustic emissions (DPOAEs) and varying levels of noise exposure history.DesignTinnitus, loudness tolerance, and speech perception ability were measured in 31 young military Veterans and 43 non-Veterans (19-35 years of age) with normal pure tone thresholds and DPOAEs. Speech perception was evaluated in quiet using NU-6 word lists and in background noise using the words in noise (WIN) test. Loudness discomfort levels were measured using 1, 3, 4, and 6 kHz pulsed pure tones. DPOAEs and ABRs were collected in each participant to assess outer hair cell (OHC) and auditory nerve function. ResultsThe probability of reporting tinnitus in this sample increased by a factor of 2.0 per 0.1 µV decrease in ABR wave I amplitude (90% Bayesian confidence interval = 1.2 to 4.2) for males and by a factor of 2.2 (90% confidence interval = 1.1 to 5.1) for females after adjusting for sex and DPOAE level. No apparent relationship was found between wave I amplitude and either loudness tolerance or speech perception in quiet or noise.ConclusionsReduced ABR wave I amplitude was associated with a markedly increased risk of tinnitus, even after adjusting for DPOAEs and sex. In contrast, wave III and V amplitudes had little effect on tinnitus risk. This suggests that changes in peripheral input at the level of the inner hair cell (IHC) or auditory nerve may lead to increases in central gain that give rise to the perception of tinnitus. Although the extent of synaptopathy in the study participants cannot be measured directly, these findings are consistent with the prediction that tinnitus may be a perceptual consequence of cochlear synaptopathy.

scholarly journals An Antibody to RGMa Promotes Regeneration of Cochlear Synapses after Noise Exposure

2020 ◽  
Author(s):  
Jerome Nevoux ◽  
Mihaela Alexandru ◽  
Thomas Bellocq ◽  
Lei Tanaka ◽  
Yushi Hayashi ◽  
...  
Keyword(s):  
Hair Cells ◽  
Noise Exposure ◽  
Auditory Brainstem ◽  
Afferent Input ◽  
Nerve Fibers ◽  
Auditory Neuropathy ◽  
Axonal Guidance ◽  
Inner Hair Cell ◽  
Inner Hair Cells ◽  
Brainstem Response

SUMMARYAuditory neuropathy is caused by the loss of afferent input to the brainstem via the components of the neural pathway comprising inner hair cells and the first order neurons of the spiral ganglion. Recent work has identified the synapse between cochlear primary afferent neurons and sensory hair cells as a particularly vulnerable component of this pathway. Loss of these synapses due to noise exposure or aging results in the pathology identified as hidden hearing loss, an initial stage of cochlear dysfunction that goes undetected in standard hearing tests. We show here that repulsive axonal guidance molecule a (RGMa) acts to prevent regrowth and synaptogenesis of peripheral auditory nerve fibers with inner hair cells. Treatment of noise-exposed animals with an anti-RGMa blocking antibody regenerated inner hair cell synapses and resulted in recovery of wave-I amplitude of the auditory brainstem response, indicating effective reversal of synaptopathy.

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