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Hearing Recovery Induced by DNA Demethylation in a Chemically Deafened Adult Mouse Model

Functional hair cell regeneration in the adult mammalian inner ear remains challenging. This study aimed to study the function of new hair cells induced by a DNA demethylating agent 5-azacytidine. Adult mice were deafened chemically, followed by injection of 5-azacytidine or vehicle into the inner e...

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Autores principales: Deng, Xin, Hu, Zhengqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891629/
https://www.ncbi.nlm.nih.gov/pubmed/35250483
http://dx.doi.org/10.3389/fncel.2022.792089
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author Deng, Xin
Hu, Zhengqing
author_facet Deng, Xin
Hu, Zhengqing
author_sort Deng, Xin
collection PubMed
description Functional hair cell regeneration in the adult mammalian inner ear remains challenging. This study aimed to study the function of new hair cells induced by a DNA demethylating agent 5-azacytidine. Adult mice were deafened chemically, followed by injection of 5-azacytidine or vehicle into the inner ear. Functionality of regenerated hair cells was evaluated by expression of hair cell proteins, auditory brainstem response (ABR), and distortion-product otoacoustic emission (DPOAE) tests for 6 weeks. In the vehicle-treated group, no cells expressed the hair cell-specific protein myosin VIIa in the cochlea, whereas numerous myosin VIIa-expressing cells were found in the 5-azacytidine-treated cochlea, suggesting the regeneration of auditory hair cells. Moreover, regenerated hair cells were co-labeled with functional proteins espin and prestin. Expression of ribbon synapse proteins suggested synapse formation between new hair cells and neurons. In hearing tests, progressive improvements in ABR [5–30 dB sound pressure level (SPL)] and DPOAE (5–20 dB) thresholds were observed in 5-azacytidine-treated mice. In vehicle-treated mice, there were <5 dB threshold changes in hearing tests. This study demonstrated the ability of 5-azacytidine to promote the functional regeneration of auditory hair cells in a mature mouse model via DNA demethylation, which may provide insights into hearing regeneration using an epigenetic approach.
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spelling pubmed-88916292022-03-04 Hearing Recovery Induced by DNA Demethylation in a Chemically Deafened Adult Mouse Model Deng, Xin Hu, Zhengqing Front Cell Neurosci Neuroscience Functional hair cell regeneration in the adult mammalian inner ear remains challenging. This study aimed to study the function of new hair cells induced by a DNA demethylating agent 5-azacytidine. Adult mice were deafened chemically, followed by injection of 5-azacytidine or vehicle into the inner ear. Functionality of regenerated hair cells was evaluated by expression of hair cell proteins, auditory brainstem response (ABR), and distortion-product otoacoustic emission (DPOAE) tests for 6 weeks. In the vehicle-treated group, no cells expressed the hair cell-specific protein myosin VIIa in the cochlea, whereas numerous myosin VIIa-expressing cells were found in the 5-azacytidine-treated cochlea, suggesting the regeneration of auditory hair cells. Moreover, regenerated hair cells were co-labeled with functional proteins espin and prestin. Expression of ribbon synapse proteins suggested synapse formation between new hair cells and neurons. In hearing tests, progressive improvements in ABR [5–30 dB sound pressure level (SPL)] and DPOAE (5–20 dB) thresholds were observed in 5-azacytidine-treated mice. In vehicle-treated mice, there were <5 dB threshold changes in hearing tests. This study demonstrated the ability of 5-azacytidine to promote the functional regeneration of auditory hair cells in a mature mouse model via DNA demethylation, which may provide insights into hearing regeneration using an epigenetic approach. Frontiers Media S.A. 2022-02-17 /pmc/articles/PMC8891629/ /pubmed/35250483 http://dx.doi.org/10.3389/fncel.2022.792089 Text en Copyright © 2022 Deng and Hu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Deng, Xin
Hu, Zhengqing
Hearing Recovery Induced by DNA Demethylation in a Chemically Deafened Adult Mouse Model
title Hearing Recovery Induced by DNA Demethylation in a Chemically Deafened Adult Mouse Model
title_full Hearing Recovery Induced by DNA Demethylation in a Chemically Deafened Adult Mouse Model
title_fullStr Hearing Recovery Induced by DNA Demethylation in a Chemically Deafened Adult Mouse Model
title_full_unstemmed Hearing Recovery Induced by DNA Demethylation in a Chemically Deafened Adult Mouse Model
title_short Hearing Recovery Induced by DNA Demethylation in a Chemically Deafened Adult Mouse Model
title_sort hearing recovery induced by dna demethylation in a chemically deafened adult mouse model
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891629/
https://www.ncbi.nlm.nih.gov/pubmed/35250483
http://dx.doi.org/10.3389/fncel.2022.792089
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