scholarly journals Endolymphatic Hydrops is a Marker of Synaptopathy Following Traumatic Noise Exposure

2021 ◽  
Vol 9 ◽  
Author(s):  
Ido Badash ◽  
Patricia M. Quiñones ◽  
Kevin J. Oghalai ◽  
Juemei Wang ◽  
Christopher G. Lui ◽  
...  
Keyword(s):  
Hair Cells ◽  
Noise Exposure ◽  
Endolymphatic Hydrops ◽  
Round Window ◽  
Acoustic Trauma ◽  
Inner Hair Cells ◽  
Speech In Noise ◽  
The Hours ◽  
Mechanistic Basis ◽  
Acute Changes

After acoustic trauma, there can be loss of synaptic connections between inner hair cells and auditory neurons in the cochlea, which may lead to hearing abnormalities including speech-in-noise difficulties, tinnitus, and hyperacusis. We have previously studied mice with blast-induced cochlear synaptopathy and found that they also developed a build-up of endolymph, termed endolymphatic hydrops. In this study, we used optical coherence tomography to measure endolymph volume in live CBA/CaJ mice exposed to various noise intensities. We quantified the number of synaptic ribbons and postsynaptic densities under the inner hair cells 1 week after noise exposure to determine if they correlated with acute changes in endolymph volume measured in the hours after the noise exposure. After 2 h of noise at an intensity of 95 dB SPL or below, both endolymph volume and synaptic counts remained normal. After exposure to 2 h of 100 dB SPL noise, mice developed endolymphatic hydrops and had reduced synaptic counts in the basal and middle regions of the cochlea. Furthermore, round-window application of hypertonic saline reduced the degree of endolymphatic hydrops that developed after 100 dB SPL noise exposure and partially prevented the reduction in synaptic counts in the cochlear base. Taken together, these results indicate that endolymphatic hydrops correlates with noise-induced cochlear synaptopathy, suggesting that these two pathologic findings have a common mechanistic basis.

scholarly journals Osmotic stabilization prevents cochlear synaptopathy after blast trauma

2018 ◽  
Vol 115 (21) ◽  
pp. E4853-E4860 ◽  
Author(s):  
Jinkyung Kim ◽  
Anping Xia ◽  
Nicolas Grillet ◽  
Brian E. Applegate ◽  
John S. Oghalai
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Hair Cells ◽  
Noise Exposure ◽  
Endolymphatic Hydrops ◽  
Surrogate Marker ◽  
Cell Loss ◽  
Hair Cell Loss ◽  
Blast Trauma

Traumatic noise causes hearing loss by damaging sensory hair cells and their auditory synapses. There are no treatments. Here, we investigated mice exposed to a blast wave approximating a roadside bomb. In vivo cochlear imaging revealed an increase in the volume of endolymph, the fluid within scala media, termed endolymphatic hydrops. Endolymphatic hydrops, hair cell loss, and cochlear synaptopathy were initiated by trauma to the mechanosensitive hair cell stereocilia and were K+-dependent. Increasing the osmolality of the adjacent perilymph treated endolymphatic hydrops and prevented synaptopathy, but did not prevent hair cell loss. Conversely, inducing endolymphatic hydrops in control mice by lowering perilymph osmolality caused cochlear synaptopathy that was glutamate-dependent, but did not cause hair cell loss. Thus, endolymphatic hydrops is a surrogate marker for synaptic bouton swelling after hair cells release excitotoxic levels of glutamate. Because osmotic stabilization prevents neural damage, it is a potential treatment to reduce hearing loss after noise exposure.

Ultrastructural Cochlear Changes following Acoustic Hyperstimulation and Ototoxicity

1976 ◽  
Vol 85 (6) ◽  
pp. 740-751 ◽  
Author(s):  
David J. Lim
Keyword(s):  
Hair Cells ◽  
Sensory Cell ◽  
Ganglion Cells ◽  
Organ Of Corti ◽  
Acoustic Trauma ◽  
Nerve Fibers ◽  
Outer Hair Cells ◽  
Type I ◽  
Cell Degeneration ◽  
Inner Hair Cells

Using guinea pigs and chinchillas as experimental animals, modes and patterns of sensory cell damage by acoustic hyperstimulation and kanamycin intoxication were compared. In general, outer hair cells were more vulnerable to both acoustic trauma and ototoxicity (particularly in the basal turn) than inner hair cells. However, in kanamycin ototoxicity, the inner hair cells were more vulnerable in the apical coil. Nerve endings and nerve fibers generally were resistant to both acoustic trauma and kanamycin intoxication, and their degeneration appears to be secondary to the sensory cell degeneration. A large number of unmyelinated nerve fibers were seen in both the organ of Corti and the osseous spiral lamina even three months after the organ of Corti had been completely degenerated by ototoxicity. The total number of unmyelinated and myelinated nerve fibers in the osseous spiral lamina far exceeded the scanty surviving ganglion cells in Rosenthal's canal, indicating the possibility of regeneration of these fibers following kanamycin intoxication. The remaining few ganglion cells were mainly type II or type III cells, and a majority of the type I ganglion cells appeared to be degenerated. Signs of strial damage were observed in both acoustic trauma and ototoxicity, but their pattern did not correlate well with that of sensory cell degeneration.

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 Endogenous SIRT3 activity is dispensable for normal hearing recovery after noise exposure in young adult mice

2020 ◽  
Author(s):  
Sally Patel ◽  
Lisa Shah ◽  
Natalie Dang ◽  
Xiaodong Tan ◽  
Anthony Almudevar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Hair Cells ◽  
Noise Exposure ◽  
Oxidative Stress Response ◽  
Outer Hair Cells ◽  
Mitochondrial Oxidative Stress ◽  
Inner Hair Cells ◽  
Hearing Recovery ◽  
Brainstem Response

ABSTRACTOccupational noise-induced hearing loss (NIHL) affects millions of people worldwide and presents a large social and personal burden. Some genetic variants in the mitochondrial oxidative stress response correlate strongly with susceptibility to NIHL in both humans and mice. Here we test the hypothesis that SIRT3, a regulator of the mitochondrial oxidative stress response, is required in mice for endogenous recovery of auditory thresholds after a sub-traumatic noise exposure. We expose homozygous Sirt3-KO mice and their wild-type littermates to a noise dose that confers a temporary threshold shift, but is not sufficient to permanently reduce cochlear function, compromise cell survival, or damage synaptic structures. We find no difference in hearing function after recovery from noise exposure between the two genotypes, when measured by either auditory brainstem response (ABR) or distortion product otoacoustic emissions (DPOAE). We show that SIRT3-specific immunoreactivity is present in outer hair cells, around the post-synaptic regions of inner hair cells, and faintly within inner hair cells. Nonetheless, outer hair cells and auditory synapses show no increase in loss after noise exposure in the homozygous Sirt3-KO mouse. These data show that SIRT3-dependent processes are not necessary for endogenous hearing recovery after a single, sub-traumatic noise exposure. They demonstrate the existence of cellular mechanisms of cochlear homeostasis in addition to the mitochondrial oxidative stress response. We also present a novel statistical analysis for identifying differences between peak 1 amplitude progressions in ABR waveforms.

Functional alteration of ribbon synapses in inner hair cells by noise exposure causing hidden hearing loss

2019 ◽  
Vol 707 ◽  
pp. 134268 ◽  
Author(s):  
Huihui Liu ◽  
Jiawen Lu ◽  
Zhongying Wang ◽  
Lei Song ◽  
Xueling Wang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Noise Exposure ◽  
Inner Hair Cells ◽  
Ribbon Synapses ◽  
Hidden Hearing Loss ◽  
Functional Alteration

scholarly journals Noise Exposure Potentiates Exocytosis From Cochlear Inner Hair Cells

2021 ◽  
Vol 13 ◽  
Author(s):  
Luis E. Boero ◽  
Shelby Payne ◽  
Maria Eugenia Gómez-Casati ◽  
Mark A. Rutherford ◽  
Juan D. Goutman
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Synaptic Vesicles ◽  
Noise Exposure ◽  
Synaptic Function ◽  
Inner Hair Cells ◽  
Distortion Product ◽  
Brainstem Response ◽  
Ganglion Neurons ◽  
Bell Shaped Curve

Noise-induced hearing loss has gained relevance as one of the most common forms of hearing impairment. The anatomical correlates of hearing loss, principally cell damage and/or death, are relatively well-understood histologically. However, much less is known about the physiological aspects of damaged, surviving cells. Here we addressed the functional consequences of noise exposure on the capacity of inner hair cells (IHCs) to release synaptic vesicles at synapses with spiral ganglion neurons (SGNs). Mice of either sex at postnatal day (P) 15–16 were exposed to 1–12 kHz noise at 120 dB sound pressure level (SPL), for 1 h. Exocytosis was measured by tracking changes in membrane capacitance (ΔCm) from IHCs of the apical cochlea. Upon IHC depolarization to different membrane potentials, ΔCm showed the typical bell-shaped curve that mirrors the voltage dependence of Ca2+ influx, in both exposed and unexposed cells. Surprisingly, from IHCs at 1-day after exposure (d.a.e.), we found potentiation of exocytosis at the peak of the bell-shaped curve. The increase in exocytosis was not accompanied by changes in whole-cell Ca2+ influx, suggesting a modification in coupling between Ca2+ channels and synaptic vesicles. Consistent with this notion, noise exposure also changed the Ca2+-dependence of exocytosis from linear to supralinear. Noise exposure did not cause loss of IHCs, but did result in a small reduction in the number of IHC-SGN synapses at 1-d.a.e. which recovered by 14-d.a.e. In contrast, a strong reduction in auditory brainstem response wave-I amplitude (representing synchronous firing of SGNs) and distortion product otoacoustic emissions (reflecting outer hair cell function) indicated a profound hearing loss at 1- and 14-d.a.e. To determine the role of glutamate release in the noise-induced potentiation of exocytosis, we evaluated vesicular glutamate transporter-3 (Vglut3) knock-out (KO) mice. Unlike WT, IHCs from Vglut3KO mice showed a noise-induced reduction in ΔCm and Ca2+ influx with no change in the Ca2+-dependence of exocytosis. Together, these results indicate that traumatic noise exposure triggers changes of IHC synaptic function including a Vglut3-dependent potentiation of exocytosis.

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.

Effect of Anesthesia on Susceptibility to Acoustic Trauma

1976 ◽  
Vol 85 (2) ◽  
pp. 276-280 ◽  
Author(s):  
Moshe Rubinstein ◽  
Nechama Pluznik
Keyword(s):  
Hair Cells ◽  
General Condition ◽  
Guinea Pigs ◽  
Pure Tone ◽  
Noise Exposure ◽  
Acoustic Trauma ◽  
Outer Hair Cells ◽  
Sensory Cells ◽  
Cochlear Hair Cells ◽  
Susceptibility To Noise

In an effort to ascertain whether differences in susceptibility to noise depend on general condition, awake and anesthetized guinea pigs were given a 4 kHz pure tone overstimulation under identical conditions. Cochlear hair cells were histologically examined four weeks after the noise exposure. The damage was localized in the upper part of the first turn and the lower part of the second turn. One fourth as much damage occurred in the anesthetized group. The distribution of damage in the four rows of sensory cells was different in the two experimental groups. In both groups of animals the damage was localized mainly to the outer hair cells, the first row sustaining the major damage.

scholarly journals C1ql1 is expressed in adult outer hair cells of the cochlea in a tonotopic gradient

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251412
Author(s):  
Joyshree Biswas ◽  
Robert S. Pijewski ◽  
Rohit Makol ◽  
Tania G. Miramontes ◽  
Brianna L. Thompson ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Noise Exposure ◽  
Outer Hair Cell ◽  
Outer Hair Cells ◽  
Conditional Knockout ◽  
Afferent Neurons ◽  
Inner Hair Cells ◽  
Afferent Synapse ◽  
The Brain

Hearing depends on the transduction of sounds into neural signals by the inner hair cells of the cochlea. Cochleae also have outer hair cells with unique electromotile properties that increase auditory sensitivity, but they are particularly susceptible to damage by intense noise exposure, ototoxic drugs, and aging. Although the outer hair cells have synapses on afferent neurons that project to the brain, the function of this neuronal circuit is unclear. Here, we created a novel mouse allele that inserts a fluorescent reporter at the C1ql1 locus which revealed gene expression in the outer hair cells and allowed creation of outer hair cell-specific C1ql1 knockout mice. We found that C1ql1 expression in outer hair cells corresponds to areas with the most sensitive frequencies of the mouse audiogram, and that it has an unexpected adolescence-onset developmental timing. No expression was observed in the inner hair cells. Since C1QL1 in the brain is made by neurons, transported anterogradely in axons, and functions in the synaptic cleft, C1QL1 may serve a similar function at the outer hair cell afferent synapse. Histological analyses revealed that C1ql1 conditional knockout cochleae may have reduced outer hair cell afferent synapse maintenance. However, auditory behavioral and physiological assays did not reveal a compelling phenotype. Nonetheless, this study identifies a potentially useful gene expressed in the cochlea and opens the door for future studies aimed at elucidating the function of C1QL1 and the function of the outer hair cell and its afferent neurons.

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