Molecular Mechanism of Tinnitus

Knipper, Marlies; Müller, Marcus; Zimmermann, Ulrike

doi:10.1007/978-1-4614-3728-4_3

Cited by 12 publications

(3 citation statements)

References 169 publications

(200 reference statements)

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“…Although hearing loss is a major risk factor for tinnitus and hyperacusis, profound evidence has meanwhile been presented showing that both tinnitus and hyperacusis can occur with (clinically) normal auditory thresholds (Geven et al 2011 ; Gu et al 2010 ; Kim et al 2011 ; Langers et al 2012 ; Lockwood et al 2002 ; Roberts et al 2010 ; Saunders 2007 ; Shiomi et al 1997 ; Tan et al 2013 ; Weisz et al 2006 ; Zeng 2013 ). As shown in animal studies, this is linked to the deafferentation of IHCs (Bauer et al 2007 ; Rüttiger et al 2013 ; Singer et al 2013 ; Tan et al 2013 ; Weisz et al 2006 ; for reviews, see Euteneuer and Praetorius 2014 ; Hébert et al 2013 ; Knipper et al 2010 , 2012 , 2013 ).…”

Section: Diverse Auditory Neuropathies Linked To Different Hearing DImentioning

confidence: 94%

Specific synaptopathies diversify brain responses and hearing disorders: you lose the gain from early life

Knipper

Panford-Walsh²,

Singer

et al. 2015

Cell Tissue Res

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Before hearing onset, inner hair cell (IHC) maturation proceeds under the influence of spontaneous Ca2+ action potentials (APs). The temporal signature of the IHC Ca2+ AP is modified through an efferent cholinergic feedback from the medial olivocochlear bundle (MOC) and drives the IHC pre- and post-synapse phenotype towards low spontaneous (spike) rate (SR), high-threshold characteristics. With sensory experience, the IHC pre- and post-synapse phenotype matures towards the instruction of low-SR, high-threshold and of high-SR, low-threshold auditory fiber characteristics. Corticosteroid feedback together with local brain-derived nerve growth factor (BDNF) and catecholaminergic neurotransmitters (dopamine) might be essential for this developmental step. In this review, we address the question of whether the control of low-SR and high-SR fiber characteristics is linked to various degrees of vulnerability of auditory fibers in the mature system. In particular, we examine several IHC synaptopathies in the context of various hearing disorders and exemplified shortfalls before and after hearing onset.

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Section: Diverse Auditory Neuropathies Linked To Different Hearing DImentioning

confidence: 94%

Specific synaptopathies diversify brain responses and hearing disorders: you lose the gain from early life

Knipper

Panford-Walsh²,

Singer

et al. 2015

Cell Tissue Res

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“…As such, peripheral auditory damage represents a primary risk factor for the generation of tinnitus, where inner hair cell (IHC) deafferentation, rather than outer hair cell (OHC) loss, is posited to play a key role in driving the disorder [ 15 – 19 ]. Animal studies have revealed that acoustic traumas, causing only transient threshold elevations can, nonetheless, cause immediate and permanent loss of cochlear ribbon synapses, which is consistent with clinical observations in which people with normal audiograms also report tinnitus [ 20 – 24 ].…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological assessment and pharmacological treatment of blast-induced tinnitus

West

et al. 2021

PLoS ONE

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Tinnitus, the phantom perception of sound, often occurs as a clinical sequela of auditory traumas. In an effort to develop an objective test and therapeutic approach for tinnitus, the present study was performed in blast-exposed rats and focused on measurements of auditory brainstem responses (ABRs), prepulse inhibition of the acoustic startle response, and presynaptic ribbon densities on cochlear inner hair cells (IHCs). Although the exact mechanism is unknown, the “central gain theory” posits that tinnitus is a perceptual indicator of abnormal increases in the gain (or neural amplification) of the central auditory system to compensate for peripheral loss of sensory input from the cochlea. Our data from vehicle-treated rats supports this rationale; namely, blast-induced cochlear synaptopathy correlated with imbalanced elevations in the ratio of centrally-derived ABR wave V amplitudes to peripherally-derived wave I amplitudes, resulting in behavioral evidence of tinnitus. Logistic regression modeling demonstrated that the ABR wave V/I amplitude ratio served as a reliable metric for objectively identifying tinnitus. Furthermore, histopathological examinations in blast-exposed rats revealed tinnitus-related changes in the expression patterns of key plasticity factors in the central auditory pathway, including chronic loss of Arc/Arg3.1 mobilization. Using a formulation of N-acetylcysteine (NAC) and disodium 2,4-disulfophenyl-N-tert-butylnitrone (HPN-07) as a therapeutic for addressing blast-induced neurodegeneration, we measured a significant treatment effect on preservation or restoration of IHC ribbon synapses, normalization of ABR wave V/I amplitude ratios, and reduced behavioral evidence of tinnitus in blast-exposed rats, all of which accorded with mitigated histopathological evidence of tinnitus-related neuropathy and maladaptive neuroplasticity.

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“…Findings from animal models however clearly suggest that it is the homeostatic mechanisms which are responsible for tinnitus generation. This is an important step forward in the understanding of tinnitus especially since the molecular mechanisms that are involved have been identified (Mazureck et al, 2010;Knipper et al, 2012). This generally believed mechanism of the generation of tinnitus also conforms to the clinical observation that in most cases the tinnitus frequency is in the same frequency area like the hearing loss.…”

mentioning

confidence: 55%

Mental Disorders - Theoretical and Empirical Perspectives

Allen¹

2013

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Molecular Mechanism of Tinnitus

Cited by 12 publications

References 169 publications

Specific synaptopathies diversify brain responses and hearing disorders: you lose the gain from early life

Specific synaptopathies diversify brain responses and hearing disorders: you lose the gain from early life

Electrophysiological assessment and pharmacological treatment of blast-induced tinnitus

Mental Disorders - Theoretical and Empirical Perspectives

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