Redox activation of excitatory pathways in auditory neurons as mechanism of age-related hearing loss
| Autor: | Rousset, Francis, Nacher-Soler, German, Coelho, Marta, Ilmjarv, Sten, Kokje, Vivianne Beatrix Christina, Marteyn, Antoine, Cambet, Yves, Perny, Michael, Roccio, Marta, Jaquet, Vincent, Senn, Pascal, Krause, Karl Heinz |
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| Přispěvatelé: | University of Zurich, Rousset, Francis |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Age-related hearing loss 610 Medicine & health 10045 Clinic for Otorhinolaryngology SV Stria Vascularis ddc:616.07 1308 Clinical Biochemistry Biochemistry CICR Ca2+ induced Ca2+ release Mice Hair Cells Auditory otorhinolaryngologic diseases Animals Humans Gene Regulatory Networks Excitotoxicity lcsh:QH301-705.5 Cells Cultured lcsh:R5-920 NADPH oxidase ARHL Age-related Hearing Loss Organic Chemistry NADPH Oxidases Presbycusis Auditory neurons OC Organ of Corti NOX NADPH oxidase Up-Regulation ddc:616.8 Glutamatergic signaling Disease Models Animal lcsh:Biology (General) Female Reactive Oxygen Species lcsh:Medicine (General) Oxidation-Reduction Research Paper ROS Reactive Oxygen Species SGN Spiral Ganglion Neurons 1605 Organic Chemistry |
| Zdroj: | Redox Biology, Vol. 30 (2020) P. 101434 Redox Biology, Vol 30, Iss, Pp-(2020) Redox Biology |
| ISSN: | 2213-2317 |
| Popis: | Age-related hearing (ARHL) loss affects a large part of the human population with a major impact on our aging societies. Yet, underlying mechanisms are not understood, and no validated therapy or prevention exists. NADPH oxidases (NOX), are important sources of reactive oxygen species (ROS) in the cochlea and might therefore be involved in the pathogenesis of ARHL. Here we investigate ARHL in a mouse model. Wild type mice showed early loss of hearing and cochlear integrity, while animals deficient in the NOX subunit p22phox remained unaffected up to six months. Genes of the excitatory pathway were down-regulated in p22phox-deficient auditory neurons. Our results demonstrate that NOX activity leads to upregulation of genes of the excitatory pathway, to excitotoxic cochlear damage, and ultimately to ARHL. In the absence of functional NOXs, aging mice conserve hearing and cochlear morphology. Our study offers new insights into pathomechanisms and future therapeutic targets of ARHL. Graphical abstract Image 1 Highlights • Mice devoid of NADPH oxidase (NOX) activity are protected from age-related hearing loss. • Cochlear NOX expression shows a similar pattern in mouse and human. • NOX3, the predominant NOX isoform in the cochlea, is mostly expressed in auditory neurons. • NOX-deficient auditory neurons show decreased transcription of glutamatergic pathway and are protected from excitotoxicity. • NOX-mediated gene regulation within auditory neurons contributes to age-related hearing loss. |
| Databáze: | OpenAIRE |
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