Phytosterols reverse antiretroviral-induced hearing loss, with potential implications for cochlear aging

Abstract: ACUho:lePslteearsoelccoonnfitrrmibtuhtaetasllthoenaeduinrgolneavel lmsaermerbeprarneseenintetedgcorirtyre,cstulyp:ports membrane protein clustering and function, and facilitates proper signal transduction. Extensive evidence has shown that cholesterol imbalances in the central nervous sy...

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Autores principales: Sodero, Alejandro O., Castagna, Valeria C., Elorza, Setiembre D., Gonzalez Rodulfo, Sara M., Paulazo, Maria Alejandra, Ballestero, Jimena A., Martin, Mauricio G., Gómez Casati, María Eugenia
Formato: Artículo
Lenguaje:Inglés
Publicado: Public Library of Science 2023
Materias:
FITOESTEROLES
COLESTEROL
OIDO
AUDICION
ENVEJECIMIENTO
PERDIDA AUDITIVA
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/17071
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-17071
record_format dspace
spelling I33-R139-123456789-170712023-09-06T05:01:15Z Phytosterols reverse antiretroviral-induced hearing loss, with potential implications for cochlear aging Sodero, Alejandro O. Castagna, Valeria C. Elorza, Setiembre D. Gonzalez Rodulfo, Sara M. Paulazo, Maria Alejandra Ballestero, Jimena A. Martin, Mauricio G. Gómez Casati, María Eugenia FITOESTEROLES COLESTEROL OIDO AUDICION ENVEJECIMIENTO PERDIDA AUDITIVA Abstract: ACUho:lePslteearsoelccoonnfitrrmibtuhtaetasllthoenaeduinrgolneavel lmsaermerbeprarneseenintetedgcorirtyre,cstulyp:ports membrane protein clustering and function, and facilitates proper signal transduction. Extensive evidence has shown that cholesterol imbalances in the central nervous system occur in aging and in the development of neurodegenerative diseases. In this work, we characterize cholesterol homeostasis in the inner ear of young and aged mice as a new unexplored possibility for the prevention and treatment of hearing loss. Our results show that cholesterol levels in the inner ear are reduced during aging, an effect that is associated with an increased expression of the cholesterol 24-hydroxylase (CYP46A1), the main enzyme responsible for cholesterol turnover in the brain. In addition, we show that pharmacological activation of CYP46A1 with the antiretroviral drug efavirenz reduces the cholesterol content in outer hair cells (OHCs), leading to a decrease in prestin immunolabeling and resulting in an increase in the distortion product otoacoustic emissions (DPOAEs) thresholds. Moreover, dietary supplementation with phytosterols, plant sterols with structure and function similar to cholesterol, was able to rescue the effect of efavirenz administration on the auditory function. Altogether, our findings point towards the importance of cholesterol homeostasis in the inner ear as an innovative therapeutic strategy in preventing and/or delaying hearing loss. 2023-09-05T19:19:57Z 2023-09-05T19:19:57Z 2023 Artículo Sodero, A. O., et al. Phytosterols reverse antiretroviral-induced hearing loss, with potential implications for cochlear aging [en línea]. PLOS Biology. 2023, 21(8) doi: 10.1371/journal.pbio.3002257. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/17071 1545-7885 (online) 1544-9173 (impreso) https://repositorio.uca.edu.ar/handle/123456789/17071 10.1371/journal.pbio.3002257 eng Acceso abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Public Library of Science PLOS Biology. 2023, 21(8)
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic FITOESTEROLES
COLESTEROL
OIDO
AUDICION
ENVEJECIMIENTO
PERDIDA AUDITIVA
spellingShingle FITOESTEROLES
COLESTEROL
OIDO
AUDICION
ENVEJECIMIENTO
PERDIDA AUDITIVA
Sodero, Alejandro O.
Castagna, Valeria C.
Elorza, Setiembre D.
Gonzalez Rodulfo, Sara M.
Paulazo, Maria Alejandra
Ballestero, Jimena A.
Martin, Mauricio G.
Gómez Casati, María Eugenia
Phytosterols reverse antiretroviral-induced hearing loss, with potential implications for cochlear aging
topic_facet FITOESTEROLES
COLESTEROL
OIDO
AUDICION
ENVEJECIMIENTO
PERDIDA AUDITIVA
description Abstract: ACUho:lePslteearsoelccoonnfitrrmibtuhtaetasllthoenaeduinrgolneavel lmsaermerbeprarneseenintetedgcorirtyre,cstulyp:ports membrane protein clustering and function, and facilitates proper signal transduction. Extensive evidence has shown that cholesterol imbalances in the central nervous system occur in aging and in the development of neurodegenerative diseases. In this work, we characterize cholesterol homeostasis in the inner ear of young and aged mice as a new unexplored possibility for the prevention and treatment of hearing loss. Our results show that cholesterol levels in the inner ear are reduced during aging, an effect that is associated with an increased expression of the cholesterol 24-hydroxylase (CYP46A1), the main enzyme responsible for cholesterol turnover in the brain. In addition, we show that pharmacological activation of CYP46A1 with the antiretroviral drug efavirenz reduces the cholesterol content in outer hair cells (OHCs), leading to a decrease in prestin immunolabeling and resulting in an increase in the distortion product otoacoustic emissions (DPOAEs) thresholds. Moreover, dietary supplementation with phytosterols, plant sterols with structure and function similar to cholesterol, was able to rescue the effect of efavirenz administration on the auditory function. Altogether, our findings point towards the importance of cholesterol homeostasis in the inner ear as an innovative therapeutic strategy in preventing and/or delaying hearing loss.
format Artículo
author Sodero, Alejandro O.
Castagna, Valeria C.
Elorza, Setiembre D.
Gonzalez Rodulfo, Sara M.
Paulazo, Maria Alejandra
Ballestero, Jimena A.
Martin, Mauricio G.
Gómez Casati, María Eugenia
author_facet Sodero, Alejandro O.
Castagna, Valeria C.
Elorza, Setiembre D.
Gonzalez Rodulfo, Sara M.
Paulazo, Maria Alejandra
Ballestero, Jimena A.
Martin, Mauricio G.
Gómez Casati, María Eugenia
author_sort Sodero, Alejandro O.
title Phytosterols reverse antiretroviral-induced hearing loss, with potential implications for cochlear aging
title_short Phytosterols reverse antiretroviral-induced hearing loss, with potential implications for cochlear aging
title_full Phytosterols reverse antiretroviral-induced hearing loss, with potential implications for cochlear aging
title_fullStr Phytosterols reverse antiretroviral-induced hearing loss, with potential implications for cochlear aging
title_full_unstemmed Phytosterols reverse antiretroviral-induced hearing loss, with potential implications for cochlear aging
title_sort phytosterols reverse antiretroviral-induced hearing loss, with potential implications for cochlear aging
publisher Public Library of Science
publishDate 2023
url https://repositorio.uca.edu.ar/handle/123456789/17071
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