Cochlear NMDA Receptors as a Therapeutic Target of Noise-Induced Tinnitus

Dai, Bing; Lee, Sze Chim; Campanelli, Dario; Xiong, Hao; Matsumoto, Masahiro; Panford-Walsh, Rama; Wolpert, Samuel M.; Praetorius, Mark; Zimmermann, Ulrike; Chu, Hanqi; Knipper, Marlies; Rüttiger, Lukas; Singer, Wibke

doi:10.1159/000374000

Cited by 59 publications

(74 citation statements)

References 58 publications

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“…The prevalence of mild tinnitus in industrial countries has been reported to be around 18% whereas 0.5% report that their tinnitus has severe negative effects on their daily life function 3 . Noise exposure has been known to be the most prevalent risk factor for developing tinnitus 4 , and it is suggested that noise-induced damage leading to tinnitus occur at the level of the inner hair cell synapse 5 . Previous studies have indicated that there is an association between the concentrations of selected stress cytokines and degrees of tinnitus severity 6 .…”

Section: Introductionmentioning

confidence: 99%

Tinnitus, Anxiety, Depression and Substance Abuse in Rock Musicians a Norwegian Survey

Størmer¹,

Sørlie²,

Stenklev³

2017

The International Tinnitus Journal

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Objective: Rock musicians are known to have an increased prevalence of hearing loss and tinnitus. The aims of the present study were to examine the distribution of anxiety and depression symptoms among rock musicians with or without tinnitus and how these mental health indicators and internal locus of control influenced upon their tinnitus symptom concerns and the degree to which the tinnitus affected their lives. Design: The study was a questionnairebased cross-sectional survey of subjects selected from a cohort of rock musicians. We recruited 111 active musicians from the Oslo region, and a control group of 40 non-musicians from the student population at the University of Tromso. Results: Among the rock musicians 19.8% reported permanent tinnitus vs. 0% among the controls. Musicians more often reported anxiety symptoms than controls (35.1% vs. 17.5%), however this prevalence was not different in musicians with and without tinnitus. Tinnitus-affected musicians reported depressive symptoms, significantly more than controls (13.6% vs. 5%). Rock musicians consumed more alcohol than controls, but alcohol consumption was unrelated to severity of tinnitus. Drug abuse was not more prevalent in rock musicians than in controls. Duration of tinnitus, internal locus of control, sleep disturbance and anxiety were significant predictors of how affected and how concerned musicians were about their tinnitus. Conclusion: Rock musicians are at risk for the development of chronic tinnitus, and they have an increased prevalence of anxiety. There is an association between chronic tinnitus and depressive symptoms in rock musicians, but our results are ambiguous. Although rock musicians have a chronic exposure to noise, noise-induced hearing loss is not the sole causative agent for the development of tinnitus.

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Section: Introductionmentioning

confidence: 99%

Tinnitus, Anxiety, Depression and Substance Abuse in Rock Musicians a Norwegian Survey

Størmer¹,

Sørlie²,

Stenklev³

2017

The International Tinnitus Journal

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“…These excitatory glutamate receptors are found in a wide range of neural cells that are responsible for opening ion channels and neural signaling. However, in the inner ear, they are found within the synapses of the inner hair cells and thought to play a role in the development of tinnitus [37]. There is significant potential for these receptors as biomarkers for neural tissues at the level of the synapse, and clinical work has already led to the identification of the therapeutic peptide Rapastinel (formally Glyx-13) as a potential therapy for tinnitus [38].…”

Section: N-methyl-d-aspartate Receptorsmentioning

confidence: 99%

“…There is significant potential for these receptors as biomarkers for neural tissues at the level of the synapse, and clinical work has already led to the identification of the therapeutic peptide Rapastinel (formally Glyx-13) as a potential therapy for tinnitus [38]. Additional work in animal models has demonstrated ribbon synapse protection from IT application of N-methyl-Daspartate (NMDA) antagonists [37].…”

Section: N-methyl-d-aspartate Receptorsmentioning

confidence: 99%

Cochlear protein biomarkers as potential sites for targeted inner ear drug delivery

Naples

Miller

Ramsey

et al. 2019

Drug Deliv. and Transl. Res.

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The delivery of therapies to the cochlea is notoriously challenging. It is an organ protected by a number of barriers that need to be overcome in the drug delivery process. Additionally, there are multiple sites of possible damage within the cochlea. Despite the many potential sites of damage, acquired otologic insults preferentially damage a single location. While progress has been made in techniques for inner ear drug delivery, the current techniques remain non-specific and our ability to deliver therapies in a cellspecific manner are limited. Fortunately, there are proteins specific to various cell-types within the cochlea (e.g., hair cells, spiral ganglion cells, stria vascularis) that function as biomarkers of site-specific damage. These protein biomarkers have potential to serve as targets for cell-specific inner ear drug delivery. In this manuscript, we review the concept of biomarkers and targetedinner ear drug delivery and the well-characterized protein biomarkers within each of the locations of interest within the cochlea. Our review will focus on targeted drug delivery in the setting of acquired otologic insults (e.g., ototoxicity, noise-induce hearing loss). The goal is not to discuss therapies to treat acquired otologic insults, rather, to establish potential concepts of how to deliver therapies in a targeted, cell-specific manner. Based on our review, it is clear that future of inner ear drug delivery is a discipline filled with potential that will require collaborative efforts among clinicians and scientists to optimize treatment of otologic insults.

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“…The treatment of hearing disorders that includes steroids [32,33], glutamate antagonist [34,35], various types of hearing aids [36][37][38], and cochlear implants [39,40]. Although these treatments produce varying degrees of improvements but they are considered unsatisfactory.…”

Section: Evidence For the Role Of Oxidative Stress In Hearing Disordersmentioning

confidence: 99%

Involvement of Oxidative Stress, Inflammation, and Glutamate in Ototoxicity, and their Attenuation by Simultaneous Activation of Nrf2 and Elevation of Antioxidant Compounds

Prasad¹,

Global²

2019

Int J Neurol Neurother

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Diverse groups of ototoxic agents and gene mutation induce hearing disorders. Several studies showed that increased oxidative stress, inflammation, and glutamate are involved in the initiation and progression of hearing disorders. Therefore, reducing these biochemical defects before and after exposure to ototoxic agents may prevent and improve the management of hearing loss. Previous studies with a single agent have yielded variable benefits in hearing disorders. This review briefly presents evidence for the involvement of oxidative stress, inflammation, and glutamate in the initiation and progression of hearing disorders. It proposes a novel concept that simultaneous elevation of the levels of antioxidant enzymes, dietary and endogenous antioxidant compounds, and reduction in the levels of glutamate may be necessary for the optimal benefits in prevention and improved management of hearing disorders. Supplementation with micronutrients can elevate the levels of antioxidant compounds and reduce the levels of glutamate. However, increasing the levels of antioxidant enzymes is complex requiring an activation of the nuclear transcriptional factor-2 (Nrf2). This review briefly describes the regulation of activation of Nrf2, and proposes a micronutrient mixture that can simultaneously activate Nrf2, enhance the dietary and endogenous antioxidant compounds levels, and inhibit the release and toxicity of glutamate for prevention and improved management of hearing loss.

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Cochlear NMDA Receptors as a Therapeutic Target of Noise-Induced Tinnitus

Cited by 59 publications

References 58 publications

Tinnitus, Anxiety, Depression and Substance Abuse in Rock Musicians a Norwegian Survey

Tinnitus, Anxiety, Depression and Substance Abuse in Rock Musicians a Norwegian Survey

Cochlear protein biomarkers as potential sites for targeted inner ear drug delivery

Involvement of Oxidative Stress, Inflammation, and Glutamate in Ototoxicity, and their Attenuation by Simultaneous Activation of Nrf2 and Elevation of Antioxidant Compounds

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