Cochlear NMDA receptors as a therapeutic target of noise-induced tinnitus

• Verfasst von: Bing, Daniel [VerfasserIn]
• Verfasst von: Lee, Sze Chim [VerfasserIn]
• Verfasst von: Campanelli, Dario [VerfasserIn]
• Verfasst von: Xiong, Hao [VerfasserIn]
• Verfasst von: Matsumoto, Masahiro [VerfasserIn]
• Verfasst von: Panford-Walsh, Rama [VerfasserIn]
• Verfasst von: Wolpert, Stephan [VerfasserIn]
• Verfasst von: Praetorius, Mark [VerfasserIn]
• Verfasst von: Zimmermann, Ulrike [VerfasserIn]
• Verfasst von: Chu, Hanqi [VerfasserIn]
• Verfasst von: Knipper, Marlies [VerfasserIn]
• Verfasst von: Rüttiger, Lukas [VerfasserIn]
• Verfasst von: Singer, Wibke [VerfasserIn]
• Titel: Cochlear NMDA receptors as a therapeutic target of noise-induced tinnitus
• Verf.angabe: Dan Bing, Sze Chim Lee, Dario Campanelli, Hao Xiong, Masahiro Matsumoto, Rama Panford-Walsh, Stephan Wolpert, Mark Praetorius, Ulrike Zimmermann, Hanqi Chu, Marlies Knipper, Lukas Rüttiger, Wibke Singer
• E-Jahr: 2015
• Jahr: March 26, 2015
• Umfang: 19 S.
• Fussnoten: Gesehen am 26.05.2020
• Titel Quelle: Enthalten in: Cellular physiology and biochemistry
• Ort Quelle: Düsseldorf : Cell Physiol Biochem Press GmbH & Co KG, 1991
• Jahr Quelle: 2015
• Band/Heft Quelle: 35(2015), 5, Seite 1905-1923
• ISSN Quelle: 1421-9778
• DOI: doi:10.1159/000374000
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1698813473

Abstract

Background: Accumulating evidence suggests that tinnitus may occur despite normal auditory sensitivity, probably linked to partial degeneration of the cochlear nerve and damage of the inner hair cell (IHC) synapse. Damage to the IHC synapses and deafferentation may occur even after moderate noise exposure. For both salicylate- and noise-induced tinnitus, aberrant N-methyl-d-aspartate (NMDA) receptor activation and related auditory nerve excitation have been suggested as origin of cochlear tinnitus. Accordingly, NMDA receptor inhibition has been proposed as a pharmacologic approach for treatment of synaptopathic tinnitus. Methods: Round-window application of the NMDA receptor antagonist AM-101 (Esketamine hydrochloride gel; Auris Medical AG, Basel, Switzerland) was tested in an animal model of tinnitus induced by acute traumatic noise. The study included the quantification of IHC ribbon synapses as a correlate for deafferentation as well as the measurement of the auditory brainstem response (ABR) to close-threshold sensation level stimuli as an indication of sound-induced auditory nerve activity. Results: We have shown that AM-101 reduced the trauma-induced loss of IHC ribbons and counteracted the decline of ABR wave I amplitude generated in the cochlea/auditory nerve. Conclusion: Local round-window application of AM-101 may be a promising therapeutic intervention for the treatment of synaptopathic tinnitus.