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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9687683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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