Identification of induced and naturally occurring conductive hearing loss in mice using bone conduction

Chhan, David; McKinnon, Melissa L.; Rosowski, John J.

doi:10.1016/j.heares.2017.02.001

Cited by 7 publications

(9 citation statements)

References 38 publications

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“…Long-term conductive hearing loss is known to lead to speech intelligibility deficits in patients and loss of synapses in an animal model of conductive hearing loss ( Liberman et al, 2015 ; Okada et al, 2020 ). Future murine studies should therefore quantify air- and bone-conduction evoked ABRs ( Qin et al, 2010 ; Chhan et al, 2017 ) to further delineate conductive vs. sensorineural contribution to HL in Coch –/– mice. In addition, future clinical studies should evaluate for potential presence of conductive hearing loss in patients with COCH pathogenic variants.…”

Section: Discussionmentioning

confidence: 99%

Cochlin Deficiency Protects Against Noise-Induced Hearing Loss

Seist

Landegger

Robertson

et al. 2021

Front. Mol. Neurosci.

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Cochlin is the most abundant protein in the inner ear. To study its function in response to noise trauma, we exposed adolescent wild-type (Coch+/+) and cochlin knock-out (Coch–/–) mice to noise (8–16 kHz, 103 dB SPL, 2 h) that causes a permanent threshold shift and hair cell loss. Two weeks after noise exposure, Coch–/– mice had substantially less elevation in noise-induced auditory thresholds and hair cell loss than Coch+/+ mice, consistent with cochlin deficiency providing protection from noise trauma. Comparison of pre-noise exposure thresholds of auditory brain stem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) in Coch–/– mice and Coch+/+ littermates revealed a small and significant elevation in thresholds of Coch–/– mice, overall consistent with a small conductive hearing loss in Coch–/– mice. We show quantitatively that the pro-inflammatory component of cochlin, LCCL, is upregulated after noise exposure in perilymph of wild-type mice compared to unexposed mice, as is the enzyme catalyzing LCCL release, aggrecanase1, encoded by Adamts4. We further show that upregulation of pro-inflammatory cytokines in perilymph and cochlear soft-tissue after noise exposure is lower in cochlin knock-out than wild-type mice. Taken together, our data demonstrate for the first time that cochlin deficiency results in conductive hearing loss that protects against physiologic and molecular effects of noise trauma.

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Section: Discussionmentioning

confidence: 99%

Cochlin Deficiency Protects Against Noise-Induced Hearing Loss

Seist

Landegger

Robertson

et al. 2021

Front. Mol. Neurosci.

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“…A hallmark of sensorineural hearing loss, widened peripheral frequency tuning, is considered a key reason for why individuals with sensorineural damage often struggle to understand speech in noisy backgrounds 49 . In contrast, CHL has been assumed to leave peripheral frequency tuning intact, based on assessments of both bottom-up input to the auditory nerve measured via bone conduction thresholds and hair cell counts 19 , 20 . Despite this, converging evidence shows that CHL (occurring either during development or adulthood) impairs speech comprehension in noise 12 – 17 .…”

Section: Discussionmentioning

confidence: 99%

“…CHL is broadly used as a model to understand how auditory deprivation affects the central auditory system as it has been assumed to leave the peripheral auditory region intact 19 , 20 . In addition to attenuating sound energy reaching the cochlea by disrupting sound transmission in the outer or middle ear, CHL can cause changes in the central auditory pathway 21 – 26 .…”

Section: Introductionmentioning

confidence: 99%

Conductive hearing loss during development does not appreciably alter the sharpness of cochlear tuning

Ihlefeld

Rosen

2021

Sci Rep

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An increasing number of studies show that listeners often have difficulty hearing in situations with background noise, despite normal tuning curves in quiet. One potential source of this difficulty could be sensorineural changes in the auditory periphery (the ear). Signal in noise detection deficits also arise in animals raised with developmental conductive hearing loss (CHL), a manipulation that induces acoustic attenuation to model how sound deprivation changes the central auditory system. This model attributes perceptual deficits to central changes by assuming that CHL does not affect sensorineural elements in the periphery that could raise masked thresholds. However, because of efferent feedback, altering the auditory system could affect cochlear elements. Indeed, recent studies show that adult-onset CHL can cause cochlear synapse loss, potentially calling into question the assumption of an intact periphery in early-onset CHL. To resolve this issue, we tested the long-term peripheral effects of CHL via developmental bilateral malleus displacement. Using forward masking tuning curves, we compared peripheral tuning in animals raised with CHL vs age-matched controls. Using compound action potential measurements from the round window, we assessed inner hair cell synapse integrity. Results indicate that developmental CHL can cause minor synaptopathy. However, developmental CHL does not appreciably alter peripheral frequency tuning.

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“…The further observation that otitis media caused similar cochlear de-efferentation and cochlear-nerve synaptopathy to that seen after TM removal ( Fig 6 ) strongly suggests that it is the loss of acoustic drive that caused the changes in cochlear efferent and afferent innervation densities, rather than some other effect of the TM surgery, such as transient acoustic trauma from manipulation of the eardrum. Further evidence is provided by the demonstration that complete TM removal in mouse causes minimal changes in bone-conduction thresholds, even when coupled with the more traumatic procedure of removing the malleus [ 36 ]. The fact that all experimental groups underwent anesthetization and minor pinna surgery on each cochlear-function test day (see Methods ) strongly suggests that it is the TM removal that caused the cochlear degeneration, rather than some less specific effect of anesthetization or surgical stress: the TM removal maneuver itself is exceedingly brief.…”

Section: Discussionmentioning

confidence: 99%

Chronic Conductive Hearing Loss Leads to Cochlear Degeneration

Liberman

Maison

2015

PLoS ONE

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Synapses between cochlear nerve terminals and hair cells are the most vulnerable elements in the inner ear in both noise-induced and age-related hearing loss, and this neuropathy is exacerbated in the absence of efferent feedback from the olivocochlear bundle. If age-related loss is dominated by a lifetime of exposure to environmental sounds, reduction of acoustic drive to the inner ear might improve cochlear preservation throughout life. To test this, we removed the tympanic membrane unilaterally in one group of young adult mice, removed the olivocochlear bundle in another group and compared their cochlear function and innervation to age-matched controls one year later. Results showed that tympanic membrane removal, and the associated threshold elevation, was counterproductive: cochlear efferent innervation was dramatically reduced, especially the lateral olivocochlear terminals to the inner hair cell area, and there was a corresponding reduction in the number of cochlear nerve synapses. This loss led to a decrease in the amplitude of the suprathreshold cochlear neural responses. Similar results were seen in two cases with conductive hearing loss due to chronic otitis media. Outer hair cell death was increased only in ears lacking medial olivocochlear innervation following olivocochlear bundle cuts. Results suggest the novel ideas that 1) the olivocochlear efferent pathway has a dramatic use-dependent plasticity even in the adult ear and 2) a component of the lingering auditory processing disorder seen in humans after persistent middle-ear infections is cochlear in origin.

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Identification of induced and naturally occurring conductive hearing loss in mice using bone conduction

Cited by 7 publications

References 38 publications

Cochlin Deficiency Protects Against Noise-Induced Hearing Loss

Cochlin Deficiency Protects Against Noise-Induced Hearing Loss

Conductive hearing loss during development does not appreciably alter the sharpness of cochlear tuning

Chronic Conductive Hearing Loss Leads to Cochlear Degeneration

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