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mTOR Signaling in BDNF-Treated Guinea Pigs after Ototoxic Deafening

The mammalian target of rapamycin (mTOR) signaling plays a critical role in cell homeostasis, growth and survival. Here, we investigated the localization of the main mTOR signaling proteins in the organ of Corti of normal-hearing and deafened guinea pigs, as well as their possible modulation by exog...

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Autores principales: Tisi, Annamaria, Ramekers, Dyan, Flati, Vincenzo, Versnel, Huib, Maccarone, Rita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687683/
https://www.ncbi.nlm.nih.gov/pubmed/36428503
http://dx.doi.org/10.3390/biomedicines10112935
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author Tisi, Annamaria
Ramekers, Dyan
Flati, Vincenzo
Versnel, Huib
Maccarone, Rita
author_facet Tisi, Annamaria
Ramekers, Dyan
Flati, Vincenzo
Versnel, Huib
Maccarone, Rita
author_sort Tisi, Annamaria
collection PubMed
description The mammalian target of rapamycin (mTOR) signaling plays a critical role in cell homeostasis, growth and survival. Here, we investigated the localization of the main mTOR signaling proteins in the organ of Corti of normal-hearing and deafened guinea pigs, as well as their possible modulation by exogenously administered brain-derived neurotrophic factor (BDNF) in deafened guinea pigs. Animals were ototoxically deafened by systemic administration of kanamycin and furosemide, and one week later, the right cochleas were treated with gelatin sponge soaked in rhBDNF, while the left cochleas were used as negative controls. Twenty-four hours after treatment, animals were euthanized, and the cochleas were processed for subsequent analysis. Through immunofluorescence, we demonstrated the localization of AKT, pAKT, mTOR, pmTOR and PTEN proteins throughout the cochlea of guinea pigs for the first time, with a higher expression in supporting cells. Moreover, an increase in mTOR immunostaining was observed in BDNF-treated cochleas by means of fluorescence intensity compared to the other groups. Conversely, Western blot analysis showed no significant differences in the protein levels between groups, probably due to dilution of proteins in the neighboring tissues of the organ of Corti. Altogether, our data indicate that mTOR signaling proteins are expressed by the organ of Corti (with a major role for supporting cells) and that the modulation of mTOR may be a protective mechanism triggered by BDNF in the degenerating organ of Corti.
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spelling pubmed-96876832022-11-25 mTOR Signaling in BDNF-Treated Guinea Pigs after Ototoxic Deafening Tisi, Annamaria Ramekers, Dyan Flati, Vincenzo Versnel, Huib Maccarone, Rita Biomedicines Article The mammalian target of rapamycin (mTOR) signaling plays a critical role in cell homeostasis, growth and survival. Here, we investigated the localization of the main mTOR signaling proteins in the organ of Corti of normal-hearing and deafened guinea pigs, as well as their possible modulation by exogenously administered brain-derived neurotrophic factor (BDNF) in deafened guinea pigs. Animals were ototoxically deafened by systemic administration of kanamycin and furosemide, and one week later, the right cochleas were treated with gelatin sponge soaked in rhBDNF, while the left cochleas were used as negative controls. Twenty-four hours after treatment, animals were euthanized, and the cochleas were processed for subsequent analysis. Through immunofluorescence, we demonstrated the localization of AKT, pAKT, mTOR, pmTOR and PTEN proteins throughout the cochlea of guinea pigs for the first time, with a higher expression in supporting cells. Moreover, an increase in mTOR immunostaining was observed in BDNF-treated cochleas by means of fluorescence intensity compared to the other groups. Conversely, Western blot analysis showed no significant differences in the protein levels between groups, probably due to dilution of proteins in the neighboring tissues of the organ of Corti. Altogether, our data indicate that mTOR signaling proteins are expressed by the organ of Corti (with a major role for supporting cells) and that the modulation of mTOR may be a protective mechanism triggered by BDNF in the degenerating organ of Corti. MDPI 2022-11-15 /pmc/articles/PMC9687683/ /pubmed/36428503 http://dx.doi.org/10.3390/biomedicines10112935 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tisi, Annamaria
Ramekers, Dyan
Flati, Vincenzo
Versnel, Huib
Maccarone, Rita
mTOR Signaling in BDNF-Treated Guinea Pigs after Ototoxic Deafening
title mTOR Signaling in BDNF-Treated Guinea Pigs after Ototoxic Deafening
title_full mTOR Signaling in BDNF-Treated Guinea Pigs after Ototoxic Deafening
title_fullStr mTOR Signaling in BDNF-Treated Guinea Pigs after Ototoxic Deafening
title_full_unstemmed mTOR Signaling in BDNF-Treated Guinea Pigs after Ototoxic Deafening
title_short mTOR Signaling in BDNF-Treated Guinea Pigs after Ototoxic Deafening
title_sort mtor signaling in bdnf-treated guinea pigs after ototoxic deafening
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687683/
https://www.ncbi.nlm.nih.gov/pubmed/36428503
http://dx.doi.org/10.3390/biomedicines10112935
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