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 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.
| Main Authors: | , , , , , , , |
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| Format: | Artículo biblioteca |
| Language: | eng |
| Published: |
Public Library of Science
2023
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| Subjects: | FITOESTEROLES, COLESTEROL, OIDO, AUDICION, ENVEJECIMIENTO, PERDIDA AUDITIVA, |
| Online Access: | https://repositorio.uca.edu.ar/handle/123456789/17071 |
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| Summary: | 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. |
|---|