scholarly journals Oncomodulin Delays Age-Related Hearing Loss in C57 and CBA Mice

2021 ◽  
Author(s):  
Leslie K Climer ◽  
Aubrey J Hornak ◽  
Kaitlin Murtha ◽  
Yang Yang ◽  
Andrew M Cox ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cell Function ◽  
Otoacoustic Emission ◽  
Auditory Brainstem ◽  
Outer Hair Cells ◽  
Distortion Product Otoacoustic Emission ◽  
Progressive Hearing Loss ◽  
Distortion Product ◽  
Age Related ◽  
Brainstem Response

Ca2+ signaling is a major contributor to sensory hair cell function in the cochlea. Oncomodulin (OCM) is a Ca2+ binding protein preferentially expressed in outer hair cells of the cochlea and few other specialized cell types. Here, we expand on our previous reports and show that OCM prevents early progressive hearing loss in mice of two different genetic backgrounds: CBA/CaJ and C57Bl/6J. In both backgrounds, genetic disruption of Ocm leads to early progressive hearing loss as measured by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). In both strains, loss of Ocm reduced hearing across lifetime (hearing span) by more than 50% relative to wild type (WT). Even though the two WT strains have very different hearing spans, OCM plays a considerable and similar role within their genetic environment to regulate hearing function. The accelerated ARHL of the Ocm KO illustrates the importance of Ca2+ signaling in maintaining hearing health.

scholarly journals Deletion of Oncomodulin Gives Rise to Early Progressive Cochlear Dysfunction in C57 and CBA Mice

2021 ◽  
Vol 13 ◽  
Author(s):  
Leslie K. Climer ◽  
Aubrey J. Hornak ◽  
Kaitlin Murtha ◽  
Yang Yang ◽  
Andrew M. Cox ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cell Function ◽  
Otoacoustic Emission ◽  
Cell Types ◽  
Auditory Brainstem ◽  
Outer Hair Cells ◽  
Distortion Product Otoacoustic Emission ◽  
Distortion Product ◽  
Age Related ◽  
Brainstem Response

Ca2+ signaling is a major contributor to sensory hair cell function in the cochlea. Oncomodulin (OCM) is a Ca2+ binding protein (CaBP) preferentially expressed in outer hair cells (OHCs) of the cochlea and few other specialized cell types. Here, we expand on our previous reports and show that OCM delays hearing loss in mice of two different genetic backgrounds: CBA/CaJ and C57Bl/6J. In both backgrounds, genetic disruption of Ocm leads to early progressive hearing loss as measured by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). In both strains, loss of Ocm reduced hearing across lifetime (hearing span) by more than 50% relative to wild type (WT). Even though the two WT strains have very different hearing spans, OCM plays a considerable and similar role within their genetic environment to regulate hearing function. The accelerated age-related hearing loss (ARHL) of the Ocm KO illustrates the importance of Ca2+ signaling in maintaining hearing health. Manipulation of OCM and Ca2+ signaling may reveal important clues to the systems of function/dysfunction that lead to ARHL.

scholarly journals Deletion of C1ql1 Causes Hearing Loss and Abnormal Auditory Nerve Fibers in the Mouse Cochlea

2021 ◽  
Vol 15 ◽  
Author(s):  
Yue Qi ◽  
Wei Xiong ◽  
Shukui Yu ◽  
Zhengde Du ◽  
Tengfei Qu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Confocal Microscopy ◽  
Auditory Brainstem ◽  
Nerve Fibers ◽  
Outer Hair Cells ◽  
Synaptic Proteins ◽  
Distortion Product Otoacoustic Emission ◽  
Distortion Product ◽  
Brainstem Response ◽  
Ganglion Neurons

Complement C1q Like 1 (C1QL1), a secreted component of C1Q-related protein, is known to play an important role in synaptic maturation, regulation, and maintenance in the central nervous system. C1ql1 is expressed in adult cochlear inner and outer hair cells (IHCs and OHCs) with preferential expression in OHCs. We generated C1ql1 null mice to examine the role of C1QL1 in the auditory periphery. C1ql1-null mice exhibited progressive hearing loss with elevated thresholds of auditory brainstem response and distortion product otoacoustic emission. Confocal microscopy showed that the number of nerve fibers innervating both IHCs and OHCs was significantly reduced. However, spiral ganglion neurons appeared to be normal under electron microscopy. IHC development and survival were not affected by deletion of C1ql1. Voltage-clamp recording and immunocytochmistry combined with confocal microscopy showed C1ql1-null IHCs showed no significant reduction of pre-synaptic proteins and synaptic vesicle release. This is in contrast to significant OHC loss in the KO mice. Our study suggests that C1ql1 is essential for development of hair cell innervation and OHC survival. But maturation of presynaptic machinery in IHCs does not depend on C1QL1.

scholarly journals Evoked Potentials Reveal Noise Exposure–Related Central Auditory Changes Despite Normal Audiograms

2020 ◽  
Vol 29 (2) ◽  
pp. 152-164 ◽  
Author(s):  
Naomi F. Bramhall ◽  
Christopher E. Niemczak ◽  
Sean D. Kampel ◽  
Curtis J. Billings ◽  
Garnett P. McMillan
Keyword(s):  
Auditory System ◽  
Noise Exposure ◽  
Otoacoustic Emission ◽  
Auditory Brainstem ◽  
Auditory Nerve Fiber ◽  
Central Auditory System ◽  
Distortion Product Otoacoustic Emission ◽  
Distortion Product ◽  
Brainstem Response ◽  
Latency Response

Purpose Complaints of auditory perceptual deficits, such as tinnitus and difficulty understanding speech in background noise, among individuals with clinically normal audiograms present a perplexing problem for audiologists. One potential explanation for these “hidden” auditory deficits is loss of the synaptic connections between the inner hair cells and their afferent auditory nerve fiber targets, a condition that has been termed cochlear synaptopathy . In animal models, cochlear synaptopathy can occur due to aging or exposure to noise or ototoxic drugs and is associated with reduced auditory brainstem response (ABR) wave I amplitudes. Decreased ABR wave I amplitudes have been demonstrated among young military Veterans and non-Veterans with a history of firearm use, suggesting that humans may also experience noise-induced synaptopathy. However, the downstream consequences of synaptopathy are unclear. Method To investigate how noise-induced reductions in wave I amplitude impact the central auditory system, the ABR, the middle latency response (MLR), and the late latency response (LLR) were measured in 65 young Veterans and non-Veterans with normal audiograms. Results In response to a click stimulus, the MLR was weaker for Veterans compared to non-Veterans, but the LLR was not reduced. In addition, low ABR wave I amplitudes were associated with a reduced MLR, but with an increased LLR. Notably, Veterans reporting tinnitus showed the largest mean LLRs. Conclusions These findings indicate that decreased peripheral auditory input leads to compensatory gain in the central auditory system, even among individuals with normal audiograms, and may impact auditory perception. This pattern of reduced MLR, but not LLR, was observed among Veterans even after statistical adjustment for sex and distortion product otoacoustic emission differences, suggesting that synaptic loss plays a role in the observed central gain. Supplemental Material https://doi.org/10.23641/asha.11977854

scholarly journals Inner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258158
Author(s):  
Neil J. Ingham ◽  
Navid Banafshe ◽  
Clarisse Panganiban ◽  
Julia L. Crunden ◽  
Jing Chen ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Cell Function ◽  
Low Frequency ◽  
Mutant Mice ◽  
Auditory Brainstem Responses ◽  
Distortion Product Otoacoustic Emission ◽  
Inner Hair Cell ◽  
Distortion Product ◽  
Age Related

Age-related hearing loss in humans (presbycusis) typically involves impairment of high frequency sensitivity before becoming progressively more severe at lower frequencies. Pathologies initially affecting lower frequency regions of hearing are less common. Here we describe a progressive, predominantly low-frequency recessive hearing impairment in two mutant mouse lines carrying different mutant alleles of the Klhl18 gene: a spontaneous missense mutation (Klhl18lowf) and a targeted mutation (Klhl18tm1a(KOMP)Wtsi). Both males and females were studied, and the two mutant lines showed similar phenotypes. Threshold for auditory brainstem responses (ABR; a measure of auditory nerve and brainstem neural activity) were normal at 3 weeks old but showed progressive increases from 4 weeks onwards. In contrast, distortion product otoacoustic emission (DPOAE) sensitivity and amplitudes (a reflection of cochlear outer hair cell function) remained normal in mutants. Electrophysiological recordings from the round window of Klhl18lowf mutants at 6 weeks old revealed 1) raised compound action potential thresholds that were similar to ABR thresholds, 2) cochlear microphonic potentials that were normal compared with wildtype and heterozygous control mice and 3) summating potentials that were reduced in amplitude compared to control mice. Scanning electron microscopy showed that Klhl18lowf mutant mice had abnormally tapering of the tips of inner hair cell stereocilia in the apical half of the cochlea while their synapses appeared normal. These results suggest that Klhl18 is necessary to maintain inner hair cell stereocilia and normal inner hair cell function at low frequencies.

Does Oral Monosodium Glutamate Have a Cochleotoxic Effect? An Experimental Study

2021 ◽  
pp. 1-13
Author(s):  
Selis Gulseven Guven ◽  
Onur Ersoy ◽  
Ruhan Deniz Topuz ◽  
Erdoğan Bulut ◽  
Gulnur Kizilay ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Outer Hair Cell ◽  
Monosodium Glutamate ◽  
Auditory Brainstem ◽  
Outer Hair Cells ◽  
Control Group ◽  
Distortion Product Otoacoustic Emission ◽  
Distortion Product ◽  
Significant Difference ◽  
Brainstem Response

<b><i>Introduction:</i></b> The effect of orally consumed monosodium glutamate (MSG), which is a common additive in the food industry, on the cochlea has not been investigated. The present study aimed to investigate the possible cochleotoxic effects of oral MSG in guinea pigs using electrophysiological, biochemical, and histopathological methods. <b><i>Methods:</i></b> Thirty guinea pigs were equally divided into control and intervention groups (MSG 100 mg/kg/day; MSG 300 mg/kg/day). At 1 month, 5 guinea pigs from each group were sacrificed; the rest were observed for another month. Electrophysiological measurements (distortion product otoacoustic emission [DPOAE] and auditory brainstem response [ABR]), glutamate levels in the perilymph and blood samples, and histopathological examinations were evaluated at 1 and 2 months. <b><i>Results:</i></b> Change in signal-to-noise ratio at 2 months was significantly different in the MSG 300 group at 0.75 kHz and 2 kHz (<i>p</i> = 0.013 and <i>p</i> = 0.044, respectively). There was no statistically significant difference in ABR wave latencies of the guinea pigs given MSG compared to the control group after 1 and 2 months; an increase was noted in ABR thresholds, although the difference was not statistically significant. In the MSG groups, moderate-to-severe degeneration and cell loss in outer hair cells, support cells, and spiral ganglia, lateral surface junction irregularities, adhesions in stereocilia, and partial loss of outer hair cell stereocilia were noted. <b><i>Conclusion:</i></b> MSG, administered in guinea pigs at a commonly utilized quantity and route of administration in humans, may be cochleotoxic.

scholarly journals Hearing Damage Induced by Blast Overpressure at Mild TBI Level in a Chinchilla Model

2020 ◽  
Vol 185 (Supplement_1) ◽  
pp. 248-255
Author(s):  
Kyle D Smith ◽  
Tao Chen ◽  
Rong Z Gan
Keyword(s):  
Auditory System ◽  
Time Course ◽  
Otoacoustic Emission ◽  
Auditory Brainstem ◽  
Distortion Product Otoacoustic Emission ◽  
Mild Tbi ◽  
Distortion Product ◽  
Blast Overpressure ◽  
Brainstem Response ◽  
Hearing Damage

Abstract Introduction The peripheral auditory system and various structures within the central auditory system are vulnerable to blast injuries, and even blast overpressure is at relatively mild traumatic brain injury (TBI) level. However, the extent of hearing loss in relation to blast number and time course of post-blast is not well understood. This study reports the progressive hearing damage measured in chinchillas after multiple blast exposures at mild TBI levels (103–138 kPa or 15–20 psi). Materials and Methods Sixteen animals (two controls) were exposed to two blasts and three blasts, respectively, in two groups with both ears plugged with foam earplugs to prevent the eardrum from rupturing. Auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) were measured in pre- and post-blasts. Immunohistochemical study of chinchilla brains were performed at the end of experiment. Results Results show that the ABR threshold and DPOAE level shifts in 2-blast animals were recovered after 7 days. In 3-blast animals, the ABR and DPOAE shifts remained at 26 and 23 dB, respectively after 14 days. Variation of auditory cortex damage between 2-blast and 3-blast was also observed in immunofluorescence images. Conclusions This study demonstrates that the number of blasts causing mild TBI critically affects hearing damage.

Thymoquinone treatment for inner-ear acoustic trauma in rats

2015 ◽  
Vol 129 (1) ◽  
pp. 38-45 ◽  
Author(s):  
F Aksoy ◽  
R Dogan ◽  
A Yenigun ◽  
B Veyseller ◽  
O Ozturan ◽  
...  
Keyword(s):  
Otoacoustic Emission ◽  
Auditory Brainstem ◽  
Acoustic Trauma ◽  
Control Group ◽  
Distortion Product Otoacoustic Emission ◽  
Distortion Product ◽  
Brainstem Response ◽  
Group 3 ◽  
Group 2 ◽  
Trauma Group

AbstractObjective:To investigate whether thymoquinone has any eliminative effects against inner-ear damage caused by acoustic trauma.Methods:Thirty-two male rats were divided into four groups. Group 1 was only exposed to acoustic trauma. Group 2 was given thymoquinone 24 hours before acoustic trauma and continued to receive it for 10 days after the trauma. Group 3 was only treated with thymoquinone, for 10 days. Group 4, the control group, suffered no trauma and received saline instead of thymoquinone. Groups 1 and 2 were exposed to acoustic trauma using 105 dB SPL white noise for 4 hours.Results:There was a significant decrease in distortion product otoacoustic emission values and an increase in auditory brainstem response thresholds in group 1 on days 1, 5 and 10, compared with baseline measurements. In group 2, a decrease in distortion product otoacoustic emission values and an increase in auditory brainstem response threshold were observed on day 1 after acoustic trauma, but measurements were comparable to baseline values on days 5 and 10. In group 3, thymoquinone had no detrimental effects on hearing. Similarly, the control group showed stable results.Conclusion:Thymoquinone was demonstrated to be a reparative rather than preventive treatment that could be used to relieve acoustic trauma.

The effect of intratympanic oxytocin treatment on rats exposed to acoustic trauma

2019 ◽  
Vol 133 (06) ◽  
pp. 466-476
Author(s):  
F C Akin Ocal ◽  
G G Kesici ◽  
S G Gurgen ◽  
R Ocal ◽  
S Erbek
Keyword(s):  
Auditory Brainstem Response ◽  
Otoacoustic Emission ◽  
Auditory Brainstem ◽  
Acoustic Trauma ◽  
Distortion Product Otoacoustic Emission ◽  
Emission Signal ◽  
Distortion Product ◽  
Brainstem Response ◽  
Group 3 ◽  
Group 1

AbstractObjectiveTo investigate whether oxytocin can prevent ototoxicity related to acoustic trauma.MethodsTwenty-eight rats were divided into four groups: noise (group 1), control (group 2), noise plus oxytocin (group 3), and oxytocin (group 4). Intratympanic oxytocin was administered on days 1, 2, 4, 6, 8 and 10 in groups 3 and 4. Groups 1 and 3 were exposed to acoustic trauma. Distortion product otoacoustic emission and auditory brainstem response testing were performed in all groups.ResultsIn group 1, auditory brainstem response thresholds increased significantly after acoustic trauma. In group 3, auditory brainstem response thresholds increased significantly on day 1 after acoustic trauma, but there were no significant differences between thresholds at baseline and on the 7th and 21st days. In group 1, significant differences were observed between distortion product otoacoustic emission signal-to-noise ratios measured before and on days 1, 7 and 21 after acoustic trauma. In group 3, no significant differences were observed between the distortion product otoacoustic emission signal-to-noise ratios measured before and on days 7 and 21 after acoustic trauma.ConclusionOxytocin had a therapeutic effect on rats exposed to acoustic trauma in this experiment.

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