1. Redox activation of excitatory pathways in auditory neurons as mechanism of age-related hearing loss
- Author
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Francis Rousset, German Nacher-Soler, Marta Coelho, Sten Ilmjarv, Vivianne Beatrix Christina Kokje, Antoine Marteyn, Yves Cambet, Michael Perny, Marta Roccio, Vincent Jaquet, Pascal Senn, and Karl Heinz Krause
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Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
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. Keywords: NADPH oxidase, Age-related hearing loss, Presbycusis, Glutamatergic signaling, Auditory neurons, Excitotoxicity
- Published
- 2020
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