scholarly journals N-Methyl-D-Aspartate Receptors Involvement in the Gentamicin-Induced Hearing Loss and Pathological Changes of Ribbon Synapse in the Mouse Cochlear Inner Hair Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Juan Hong ◽  
Yan Chen ◽  
Yanping Zhang ◽  
Jieying Li ◽  
Liujie Ren ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Auditory Brainstem ◽  
Ribbon Synapse ◽  
Synaptic Ribbons ◽  
Pathological Changes ◽  
Inner Hair Cell ◽  
Ribbon Synapses ◽  
Brainstem Response ◽  
Mature Mouse ◽  
Response Thresholds

Cochlear inner hair cell (IHC) ribbon synapses play an important role in sound encoding and neurotransmitter release. Previous reports show that both noise and aminoglycoside exposures lead to reduced numbers and morphologic changes of synaptic ribbons. In this work, we determined the distribution of N-methyl-D-aspartate receptors (NMDARs) and their role in the gentamicin-induced pathological changes of cochlear IHC ribbon synaptic elements. In normal mature mouse cochleae, the majority of NMDARs were distributed on the modiolar side of IHCs and close to the IHC nuclei region, while most of synaptic ribbons and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) were located on neural terminals closer to the IHC basal poles. After gentamicin exposure, the NMDARs increased and moved towards the IHC basal poles. At the same time, synaptic ribbons and AMPARs moved toward the IHC bundle poles on the afferent dendrites. The number of ribbon synapse decreased, and this was accompanied by increased auditory brainstem response thresholds and reduced wave I amplitudes. NMDAR antagonist MK801 treatment reduced the gentamicin-induced hearing loss and the pathological changes of IHC ribbon synapse, suggesting that NMDARs were involved in gentamicin-induced ototoxicity by regulating the number and distribution of IHC ribbon synapses.

scholarly journals Loss of Cochlear Ribbon Synapse Is a Critical Contributor to Chronic Salicylate Sodium Treatment-Induced Tinnitus without Change Hearing Threshold

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Zhang ◽  
Zhe Peng ◽  
ShuKui Yu ◽  
Qing-Ling Song ◽  
Teng-Fei Qu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Hearing Threshold ◽  
Significant Loss ◽  
Acoustic Startle Reflex ◽  
Ribbon Synapse ◽  
Inner Hair Cell ◽  
Adult Rats ◽  
Ribbon Synapses

Tinnitus is a common auditory disease worldwide; it is estimated that more than 10% of all individuals experience this hearing disorder during their lifetime. Tinnitus is sometimes accompanied by hearing loss. However, hearing loss is not acquired in some other tinnitus generations. In this study, we injected adult rats with salicylate sodium (SS) (200 mg/kg/day for 10 days) and found no significant hearing threshold changes at 2, 4, 8, 12, 14, 16, 20, or 24 kHz (all p>0.05). Tinnitus was confirmed in the treated rats via Behaviour Testing of Acoustic Startle Response (ASR) and Gap Prepulse Inhibition Test of Acoustic Startle Reflex (GPIAS). A immunostaining study showed that there is significant loss of anti-CtBP2 puncta (a marker of cochlear inner hair cell (HC) ribbon synapses) in treated animals in apical, middle, and basal turns (all p<0.05). The ABR wave I amplitudes were significantly reduced at 4, 8, 12, 14, 16, and 20 kHz (all p<0.05). No significant losses of outer HCs, inner HCs, or HC cilia were observed (all p>0.05). Thus, our study suggests that loss of cochlear inner HC ribbon synapse after SS exposure is a contributor to the development of tinnitus without changing hearing threshold.

scholarly journals Synaptic Release Potentiation at Aging Auditory Ribbon Synapses

2021 ◽  
Vol 13 ◽  
Author(s):  
Thibault Peineau ◽  
Séverin Belleudy ◽  
Susanna Pietropaolo ◽  
Yohan Bouleau ◽  
Didier Dulon
Keyword(s):  
Hearing Loss ◽  
Acoustic Startle ◽  
Auditory Brainstem ◽  
Bk Channels ◽  
Acoustic Startle Reflex ◽  
Inner Hair Cell ◽  
Functional Changes ◽  
Ribbon Synapses ◽  
Age Related ◽  
Cadherin 23

Age-related hidden hearing loss is often described as a cochlear synaptopathy that results from a progressive degeneration of the inner hair cell (IHC) ribbon synapses. The functional changes occurring at these synapses during aging are not fully understood. Here, we characterized this aging process in IHCs of C57BL/6J mice, a strain which is known to carry a cadherin-23 mutation and experiences early hearing loss with age. These mice, while displaying a large increase in auditory brainstem thresholds due to 50% loss of IHC synaptic ribbons at middle age (postnatal day 365), paradoxically showed enhanced acoustic startle reflex suggesting a hyperacusis-like response. The auditory defect was associated with a large shrinkage of the IHCs' cell body and a drastic enlargement of their remaining presynaptic ribbons which were facing enlarged postsynaptic AMPAR clusters. Presynaptic Ca2+ microdomains and the capacity of IHCs to sustain high rates of exocytosis were largely increased, while on the contrary the expression of the fast-repolarizing BK channels, known to negatively control transmitter release, was decreased. This age-related synaptic plasticity in IHCs suggested a functional potentiation of synaptic transmission at the surviving synapses, a process that could partially compensate the decrease in synapse number and underlie hyperacusis.

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 Hidden hearing loss is associated with loss of ribbon synapses of cochlea inner hair cells

2021 ◽  
Author(s):  
Feng Song ◽  
Bin Gan ◽  
Na Wang ◽  
Zhe Wang ◽  
An-ting Xu
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Noise Exposure ◽  
Repeated Exposure ◽  
Ribbon Synapse ◽  
Intensity Noise ◽  
Auditory Function ◽  
Ribbon Synapses ◽  
Brainstem Response ◽  
Hidden Hearing Loss

This study aimed to observe the changes in the cochlea ribbon synapses after repeated exposure to moderate-to-high intensity noise. Guinea pigs received 95 dB SPL white noise exposure 4 hours a day for consecutive 7 days (we regarded it a medium-term and moderate-intensity noise, or MTMI noise). Animals were divided into 4 groups: Control, 1DPN (1-day post noise), 1WPN (1-week post noise), and 1MPN (1-month post noise). Auditory function analysis by ABR and CAP recordings, as well as ribbon synapse morphological analyses by immunohistochemistry (Ctbp2 and PSD95 staining) were performed one day, one week, and one month after noise exposure. After MTMI noise exposure, the amplitudes of auditory brainstem response (ABR) I and III waves were suppressed. The compound action potential (CAP) threshold was elevated, and CAP amplitude was reduced in the 1DPN group. No apparent changes in hair cell shape, arrangement or number were observed, but the number of ribbon synapse was reduced. The 1WPN and 1MPN groups showed that part of ABR and CAP changes recovered, as well as the synapse number. The defects in cochlea auditory function and synapse changes were observed mainly in the high-frequency region. Together, repeated exposure in MTMI noise can cause hidden hearing loss, which is partially reversible after leaving the noise environment; and MTMI noise induced hidden hearing loss is associated with inner hair cell ribbon synapses.

Perinatal hypoxia and auditory brainstem response thresholds: No evidence of permanent hearing loss

1988 ◽  
Vol 33 (3) ◽  
pp. 239-244 ◽  
Author(s):  
Yael Cycowicz ◽  
Michal Schmuel ◽  
Sharon Freeman ◽  
Alan Wanszelbaum ◽  
Haim Sohmer
Keyword(s):  
Hearing Loss ◽  
Auditory Brainstem Response ◽  
Auditory Brainstem ◽  
Perinatal Hypoxia ◽  
Brainstem Response ◽  
Response Thresholds

scholarly journals VGLUT3-p.A211V variant fuses stereocilia bundle and elongates synaptic ribbons in the human deafness DFNA25

2020 ◽  
Author(s):  
Yuvraj Joshi ◽  
Stéphanie Miot ◽  
Marie Guillet ◽  
Gaston Sendin ◽  
Jérôme Bourien ◽  
...  
Keyword(s):  
Otoacoustic Emissions ◽  
Glutamate Transporter ◽  
Super Resolution ◽  
Auditory Brainstem ◽  
Synaptic Ribbons ◽  
Primary Defect ◽  
Ribbon Synapses ◽  
Distortion Products ◽  
Brainstem Response ◽  
Type 3

DFNA25 is an autosomal-dominant and progressive form of human deafness caused by mutations in the SLC17A8 gene, which encodes the vesicular glutamate transporter type 3 (VGLUT3). To resolve the mechanisms underlying DFNA25, we studied the phenotype of the mouse harboring the p.A221V mutation in human (corresponding to p.A224V in mouse). Using auditory brainstem response and distortion products of otoacoustic emissions, we showed that VGLUT3A224V/A224V mouse replicates the DFNA25 progressive hearing loss with intact cochlear amplification. Scanning electron microscopy examinations demonstrated fused stereocilia bundle of the inner hair cells (IHCs) as the primary cause for DFNA25. In addition, the IHC ribbon synapses undergo structural and functional modifications at later stages. Using super-resolution microscopy, we observed oversized synaptic ribbons associated with an increase in the rate of the sustained releasable pool of exocytosis. These results indicate that the primary defect in DFNA25 stems from a failure in the mechano-transduction followed by a change in synaptic transfer. The VGLUT3A224V/A224V mouse model opens the way to a deeper understanding and to a potential treatment of DFNA25.

Glutathione Ester But Not Glutathione Protects Against Cisplatin-Induced Ototoxicity in a Rat Model

2003 ◽  
Vol 14 (03) ◽  
pp. 124-133 ◽  
Author(s):  
Kathleen C.M. Campbell ◽  
Deb L. Larsen ◽  
Robert P. Meech ◽  
Leonard P. Rybak ◽  
Larry F. Hughes
Keyword(s):  
Auditory Brainstem Response ◽  
Outer Hair Cell ◽  
Tone Burst ◽  
Auditory Brainstem ◽  
Control Group ◽  
Brainstem Response ◽  
Group A ◽  
Direct Administration ◽  
Response Thresholds ◽  
Para Determinar

Glutathione (GSH) provides an important antioxidant and detoxification pathway. We tested to determine if direct administration of GSH or GSH ester could reduce cisplatin- (CDDP) induced ototoxicity. We tested eight groups of five rats each: a control group, a group receiving 16 mg/kg ip CDDP infused over 30 minutes, and six groups receiving either GSH or GSH ester at 500, 1000, or 1500 mg/kg intraperitoneally 30 minutes prior to 16 mg/kg CDDP. Auditory brainstem response thresholds were measured for click and tone-burst stimuli at baseline and 3 days later. Outer hair cell (OHC) loss was measured for the apical, middle and basal turns. The 500 mg/kg GSH ester reduced hearing loss and OHC loss, but protection decreased as dosage increased, suggesting possible toxicity. GSH was not significantly protective. The best GSH ester protection was less than we have previously reported with D-methionine. El glutatión (GSH) brinda una importante vía antioxidante y de cetoxificación. Realizamos una prueba para determinar si la administración directa de GSH o del éster de GSH podía reducir la ototoxicidad inducida por cisplatino (CDDP). Hicimos una evaluación en ocho grupos de cinco ratas cada uno: un grupo control, un grupo que recibió CDDP intraperitoneal a 16 mg/kg en una ínfusión durante 30 minutos y seis grupos que recibieron intraperitonealmente GSH o el éster de GSH a 500, 1000 o 1500 mg/kg, 30 minutos antes del CDDP a 16 mg/kg. Se midieron umbrales de respuestas auditivas del tallo cerebral tanto para clicks como para bursts tonales, al inicio y 3 días después. La pérdida de células ciliadas externas (OHC) fue establecida a nivel de las vueltas apical, media y basal. La dosis de 500 mg/kg de éster de GSH redujo la hipoacusia y la pérdida de OHC, pero la protección disminuyó conforme la dosis se incrementó, sugiriendo una posible toxicidad. EL GSH no resultó significativamente protector. El mejor efecto protector del éster de GSH fue menor que el previamente reportado con D-Metionina.

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