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 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 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.

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 Analysis of Chronic Tinnitus in Noise-Induced Hearing Loss and Presbycusis

2021 ◽  
Vol 10 (8) ◽  
pp. 1779
Author(s):  
Hee Jin Kang ◽  
Dae Woong Kang ◽  
Sung Su Kim ◽  
Tong In Oh ◽  
Sang Hoon Kim ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Otoacoustic Emissions ◽  
Pure Tone Audiometry ◽  
Auditory Brainstem ◽  
Outer Hair Cells ◽  
Chronic Tinnitus ◽  
Noise Induced Hearing Loss ◽  
Distortion Product ◽  
Hearing Thresholds ◽  
Brainstem Response

The most frequent causes of tinnitus associated with hearing loss are noise-induced hearing loss and presbycusis. The mechanism of tinnitus is not yet clear, although several hypotheses have been suggested. Therefore, we aimed to analyze characteristics of chronic tinnitus between noise-induced hearing loss and presbycusis. Materials and Methods: This paper is a retrospective chart review and outpatient clinic-based study of 248 patients with chronic tinnitus from 2015 to 2020 with noise-induced or presbycusis. Pure tone audiometry (PTA), auditory brainstem response (ABR), distortion product otoacoustic emissions (DPOAE), transient evoked otoacoustic emissions (TEOAE), and tinnitograms were conducted. Results: PTA showed that hearing thresholds at all frequencies were higher in patients with noise-induced hearing loss than the presbycusis group. ABR tests showed that patients with presbycusis had longer wave I and III latencies (p < 0.05 each) than patients with noise-induced hearing loss. TEOAE tests showed lower values in patients with noise-induced hearing loss than presbycusis at 1.5, 2, 3, and 4 kHz (p < 0.05 each). DPOAE tests showed that response rates in both ears at 1.5, 2, and 3 kHz were significantly higher in patients with presbycusis than noise-induced hearing loss (p < 0.05 each). Discussion: This study showed that hearing thresholds were higher, the loudness of tinnitus was smaller, and the degree of damage to outer hair cells was lower in patients with presbycusis than with noise-induced hearing loss. Moreover, wave I and III latencies were more prolonged in patients with presbycusis despite their having lower hearing thresholds. These phenomena may reflect the effects of aging or degeneration of the central nervous system with age. Further studies are needed to evaluate the etiologies of tinnitus.

Methionine Sulfoxide Reductase A Knockout Mice Show Progressive Hearing Loss and Sensitivity to Acoustic Trauma

2018 ◽  
Vol 23 (1) ◽  
pp. 20-31 ◽  
Author(s):  
Safa Alqudah ◽  
Mark Chertoff ◽  
Dianne Durham ◽  
Jackob Moskovitz ◽  
Hinrich Staecker ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Knockout Mice ◽  
Noise Exposure ◽  
Methionine Sulfoxide ◽  
Auditory Brainstem ◽  
Acoustic Trauma ◽  
Methionine Sulfoxide Reductase ◽  
Distortion Product Otoacoustic Emission ◽  
Distortion Product ◽  
Brainstem Response

Methionine sulfoxide reductases (MsrA and MsrB) protect the biological activity of proteins from oxidative modifications to methionine residues and are important for protecting against the pathological effects of neurodegenerative diseases. In the current study, we characterized the auditory phenotype of the MsrA knockout mouse. Young MsrA knockout mice showed small high-frequency threshold elevations for auditory brainstem response and distortion product otoacoustic emission compared to those of wild-type mice, which progressively worsened in older MsrA knockout mice. MsrA knockout mice showed an increased sensitivity to noise at young and older ages, suggesting that MsrA is part of a mechanism that protects the cochlea from acoustic damage. MsrA mRNA in the cochlea was increased following acoustic stimulation. Finally, expression of mRNA MsrB1 was compromised at 6 months old, but not in younger MsrA knockout mice (compared to controls). The identification of MsrA in the cochlea as a protective mediator from both early onset hearing loss and acoustic trauma expands our understanding of the pathways that may induce protection from acoustic trauma and foster further studies on how to prevent the damaging effect of noise exposure through Msr-based therapy.

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 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.

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