Preventing presbycusis in mice with enhanced medial olivocochlear feedback
Author | dc.contributor.author | Boero, Luis E. | |
Author | dc.contributor.author | Castagna, Valeria C. | |
Author | dc.contributor.author | Terreros, Gonzalo | |
Author | dc.contributor.author | Moglie, Marcelo J. | |
Author | dc.contributor.author | Silva, Sebastián | |
Author | dc.contributor.author | Maass Oñate, Juan | |
Author | dc.contributor.author | Fuchs, Paul A. | |
Author | dc.contributor.author | Délano, Paul H. | |
Author | dc.contributor.author | Elgoyhen, Ana Belén | |
Author | dc.contributor.author | Gómez Casati, María Eugenia | |
Admission date | dc.date.accessioned | 2020-07-02T15:10:31Z | |
Available date | dc.date.available | 2020-07-02T15:10:31Z | |
Publication date | dc.date.issued | 2020 | |
Cita de ítem | dc.identifier.citation | PNAS | May 26, 2020 | vol. 117 | no. 21 | 11811–11819 | es_ES |
Identifier | dc.identifier.other | 10.1073/pnas.2000760117 | |
Identifier | dc.identifier.uri | https://repositorio.uchile.cl/handle/2250/175752 | |
Abstract | dc.description.abstract | "Growing old" is the most common cause of hearing loss. Age-related hearing loss (ARHL) (presbycusis) first affects the ability to understand speech in background noise, even when auditory thresholds in quiet are normal. It has been suggested that cochlear denervation ("synaptopathy") is an early contributor to age-related auditory decline. In the present work, we characterized age-related cochlear synaptic degeneration and hair cell loss in mice with enhanced alpha 9 alpha 10 cholinergic nicotinic receptors gating kinetics ("gain of function" nAChRs). These mediate inhibitory olivocochlear feedback through the activation of associated calcium-gated potassium channels. Cochlear function was assessed via distortion product otoacoustic emissions and auditory brainstem responses. Cochlear structure was characterized in immunolabeled organ of Corti whole mounts using confocal microscopy to quantify hair cells, auditory neurons, presynaptic ribbons, and postsynaptic glutamate receptors. Aged wild-type mice had elevated acoustic thresholds and synaptic loss. Afferent synapses were lost from inner hair cells throughout the aged cochlea, together with some loss of outer hair cells. In contrast, cochlear structure and function were preserved in aged mice with gain-of-function nAChRs that provide enhanced olivocochlear inhibition, suggesting that efferent feedback is important for long-term maintenance of inner ear function. Our work provides evidence that olivocochlear-mediated resistance to presbycusis-ARHL occurs via the alpha 9 alpha 10 nAChR complexes on outer hair cells. Thus, enhancement of the medial olivocochlear system could be a viable strategy to prevent age-related hearing loss. | es_ES |
Patrocinador | dc.description.sponsorship | ANPCyT Pew Charitable Trusts (United States) National Organization for Hearing Research (United States) United States Department of Health & Human Services National Institutes of Health (NIH) - USA R01 DC001508 Fondation Pour L'Audition (France) Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1161155 Comision Nacional de Investigacion Cientifica y Tecnologica BASAL from Centro de Avanzado de Ingenieria Electrica y Electronica (Chile) FB008 Instituto de Neurociencia Biomedica (Chile) P09-015F Proyecto REDES (Chile) 150134 Fondos de Movilidad Institucional Universidad de O'Higgins (Chile) Fundacion Guillermo Puelma (Chile) | es_ES |
Lenguage | dc.language.iso | en | es_ES |
Publisher | dc.publisher | National Academy of Sciences | es_ES |
Type of license | dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Chile | * |
Link to License | dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/cl/ | * |
Source | dc.source | Proceedings of the National Academy of Sciences of the United States of America | es_ES |
Keywords | dc.subject | Hearing loss | es_ES |
Keywords | dc.subject | Aging | es_ES |
Keywords | dc.subject | Cochlear synaptopathy | es_ES |
Keywords | dc.subject | Medial olivocochlear system | es_ES |
Título | dc.title | Preventing presbycusis in mice with enhanced medial olivocochlear feedback | es_ES |
Document type | dc.type | Artículo de revista | es_ES |
dcterms.accessRights | dcterms.accessRights | Acceso Abierto | |
Cataloguer | uchile.catalogador | laj | es_ES |
Indexation | uchile.index | Artículo de publicación ISI | |
Indexation | uchile.index | Artículo de publicación SCOPUS |
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