Preventing presbycusis in mice with enhanced medial olivocochlear feedback

Autores
Boero, Luis Ezequiel; Castagna, Valeria Carolina; Terreros, Gonzalo; Moglie, Marcelo Javier; Silva, Sebastián; Maass, Juan C.; Fuchs, Paul A.; Delano, Paul H.; Elgoyhen, Ana Belen; Gomez Casati, Maria Eugenia
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
"Growing old" is the most common cause of hearing loss. Agerelated 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 agerelated auditory decline. In the present work, we characterized age-related cochlear synaptic degeneration and hair cell loss in mice with enhanced α9α10 cholinergic nicotinic receptors gating kinetics ("gain of function" nAChRs). These mediate inhibitory olivocochlear feedback through the activation of associated calciumgated 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 α9α10 nAChR complexes on outer hair cells. Thus, enhancement of the medial olivocochlear system could be a viable strategy to prevent age-related hearing loss.
Fil: Boero, Luis Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; Argentina
Fil: Castagna, Valeria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; Argentina
Fil: Terreros, Gonzalo. Universidad de Chile; Chile
Fil: Moglie, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Silva, Sebastián. Universidad de Chile; Chile
Fil: Maass, Juan C.. Universidad de Chile; Chile
Fil: Fuchs, Paul A.. University Johns Hopkins; Estados Unidos
Fil: Delano, Paul H.. Universidad de Chile; Chile
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; Argentina
Fil: Gomez Casati, Maria Eugenia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Materia
AGING
COCHLEAR SYNAPTOPATHY
HEARING LOSS
MEDIAL OLIVOCOCHLEAR SYSTEM
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/138061
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Preventing presbycusis in mice with enhanced medial olivocochlear feedbackBoero, Luis EzequielCastagna, Valeria CarolinaTerreros, GonzaloMoglie, Marcelo JavierSilva, SebastiánMaass, Juan C.Fuchs, Paul A.Delano, Paul H.Elgoyhen, Ana BelenGomez Casati, Maria EugeniaAGINGCOCHLEAR SYNAPTOPATHYHEARING LOSSMEDIAL OLIVOCOCHLEAR SYSTEMhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3"Growing old" is the most common cause of hearing loss. Agerelated 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 agerelated auditory decline. In the present work, we characterized age-related cochlear synaptic degeneration and hair cell loss in mice with enhanced α9α10 cholinergic nicotinic receptors gating kinetics ("gain of function" nAChRs). These mediate inhibitory olivocochlear feedback through the activation of associated calciumgated 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 α9α10 nAChR complexes on outer hair cells. Thus, enhancement of the medial olivocochlear system could be a viable strategy to prevent age-related hearing loss.Fil: Boero, Luis Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; ArgentinaFil: Castagna, Valeria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; ArgentinaFil: Terreros, Gonzalo. Universidad de Chile; ChileFil: Moglie, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Silva, Sebastián. Universidad de Chile; ChileFil: Maass, Juan C.. Universidad de Chile; ChileFil: Fuchs, Paul A.. University Johns Hopkins; Estados UnidosFil: Delano, Paul H.. Universidad de Chile; ChileFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; ArgentinaFil: Gomez Casati, Maria Eugenia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaNational Academy of Sciences2020-05-26info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/138061Boero, Luis Ezequiel; Castagna, Valeria Carolina; Terreros, Gonzalo; Moglie, Marcelo Javier; Silva, Sebastián; et al.; Preventing presbycusis in mice with enhanced medial olivocochlear feedback; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 117; 21; 26-5-2020; 11811-118190027-84241091-6490CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/lookup/doi/10.1073/pnas.2000760117info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.2000760117info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:39:15Zoai:ri.conicet.gov.ar:11336/138061instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:39:15.725CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Preventing presbycusis in mice with enhanced medial olivocochlear feedback
title Preventing presbycusis in mice with enhanced medial olivocochlear feedback
spellingShingle Preventing presbycusis in mice with enhanced medial olivocochlear feedback
Boero, Luis Ezequiel
AGING
COCHLEAR SYNAPTOPATHY
HEARING LOSS
MEDIAL OLIVOCOCHLEAR SYSTEM
title_short Preventing presbycusis in mice with enhanced medial olivocochlear feedback
title_full Preventing presbycusis in mice with enhanced medial olivocochlear feedback
title_fullStr Preventing presbycusis in mice with enhanced medial olivocochlear feedback
title_full_unstemmed Preventing presbycusis in mice with enhanced medial olivocochlear feedback
title_sort Preventing presbycusis in mice with enhanced medial olivocochlear feedback
dc.creator.none.fl_str_mv Boero, Luis Ezequiel
Castagna, Valeria Carolina
Terreros, Gonzalo
Moglie, Marcelo Javier
Silva, Sebastián
Maass, Juan C.
Fuchs, Paul A.
Delano, Paul H.
Elgoyhen, Ana Belen
Gomez Casati, Maria Eugenia
author Boero, Luis Ezequiel
author_facet Boero, Luis Ezequiel
Castagna, Valeria Carolina
Terreros, Gonzalo
Moglie, Marcelo Javier
Silva, Sebastián
Maass, Juan C.
Fuchs, Paul A.
Delano, Paul H.
Elgoyhen, Ana Belen
Gomez Casati, Maria Eugenia
author_role author
author2 Castagna, Valeria Carolina
Terreros, Gonzalo
Moglie, Marcelo Javier
Silva, Sebastián
Maass, Juan C.
Fuchs, Paul A.
Delano, Paul H.
Elgoyhen, Ana Belen
Gomez Casati, Maria Eugenia
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AGING
COCHLEAR SYNAPTOPATHY
HEARING LOSS
MEDIAL OLIVOCOCHLEAR SYSTEM
topic AGING
COCHLEAR SYNAPTOPATHY
HEARING LOSS
MEDIAL OLIVOCOCHLEAR SYSTEM
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv "Growing old" is the most common cause of hearing loss. Agerelated 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 agerelated auditory decline. In the present work, we characterized age-related cochlear synaptic degeneration and hair cell loss in mice with enhanced α9α10 cholinergic nicotinic receptors gating kinetics ("gain of function" nAChRs). These mediate inhibitory olivocochlear feedback through the activation of associated calciumgated 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 α9α10 nAChR complexes on outer hair cells. Thus, enhancement of the medial olivocochlear system could be a viable strategy to prevent age-related hearing loss.
Fil: Boero, Luis Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; Argentina
Fil: Castagna, Valeria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; Argentina
Fil: Terreros, Gonzalo. Universidad de Chile; Chile
Fil: Moglie, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Silva, Sebastián. Universidad de Chile; Chile
Fil: Maass, Juan C.. Universidad de Chile; Chile
Fil: Fuchs, Paul A.. University Johns Hopkins; Estados Unidos
Fil: Delano, Paul H.. Universidad de Chile; Chile
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; Argentina
Fil: Gomez Casati, Maria Eugenia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
description "Growing old" is the most common cause of hearing loss. Agerelated 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 agerelated auditory decline. In the present work, we characterized age-related cochlear synaptic degeneration and hair cell loss in mice with enhanced α9α10 cholinergic nicotinic receptors gating kinetics ("gain of function" nAChRs). These mediate inhibitory olivocochlear feedback through the activation of associated calciumgated 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 α9α10 nAChR complexes on outer hair cells. Thus, enhancement of the medial olivocochlear system could be a viable strategy to prevent age-related hearing loss.
publishDate 2020
dc.date.none.fl_str_mv 2020-05-26
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/138061
Boero, Luis Ezequiel; Castagna, Valeria Carolina; Terreros, Gonzalo; Moglie, Marcelo Javier; Silva, Sebastián; et al.; Preventing presbycusis in mice with enhanced medial olivocochlear feedback; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 117; 21; 26-5-2020; 11811-11819
0027-8424
1091-6490
CONICET Digital
CONICET
url http://hdl.handle.net/11336/138061
identifier_str_mv Boero, Luis Ezequiel; Castagna, Valeria Carolina; Terreros, Gonzalo; Moglie, Marcelo Javier; Silva, Sebastián; et al.; Preventing presbycusis in mice with enhanced medial olivocochlear feedback; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 117; 21; 26-5-2020; 11811-11819
0027-8424
1091-6490
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/lookup/doi/10.1073/pnas.2000760117
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.2000760117
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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