Artículo
Phytosterols reverse antiretroviral-induced hearing loss, with potential implications for cochlear aging
Sodero, Alejandro Omar
; Castagna, Valeria Carolina
; Elorza, Setiembre Delfina; Gonzalez Rodulfo, Sara Margarita
; Paulazo, Maria Alejandra
; Ballestero, Jimena Andrea
; Martín, Mauricio Gerardo
; Gomez Casati, Maria Eugenia
Fecha de publicación:
08/2023
Editorial:
Public Library of Science
Revista:
PLoS Biology
ISSN:
1544-9173
e-ISSN:
1545-7885
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
AU Cholesterol: Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly contributes to neuronal membrane integrity, supports : 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.
Palabras clave:
Cholesterol
,
Cochlea
,
Phytosterols
,
Hearing loss
,
Aging
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Colecciones
Articulos(BIOMED)
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Articulos(INGEBI)
Articulos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Articulos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Articulos(INIMEC - CONICET)
Articulos de INSTITUTO DE INV. MEDICAS MERCEDES Y MARTIN FERREYRA
Articulos de INSTITUTO DE INV. MEDICAS MERCEDES Y MARTIN FERREYRA
Citación
Sodero, Alejandro Omar; Castagna, Valeria Carolina; Elorza, Setiembre Delfina; Gonzalez Rodulfo, Sara Margarita; Paulazo, Maria Alejandra; et al.; Phytosterols reverse antiretroviral-induced hearing loss, with potential implications for cochlear aging; Public Library of Science; PLoS Biology; 21; 8; 8-2023; 1-22
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