Exacerbated age-related hearing loss in mice lacking the p43 mitochondrial T3 receptor
Abstract Background Age-related hearing loss (ARHL), also known as presbycusis, is the most common sensory impairment seen in elderly people. However, the cochlear aging process does not affect people uniformly, suggesting that both genetic and environmental (e.g., noise, ototoxic drugs) factors and...
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| Format: | Article |
| Language: | English |
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BMC
2021-02-01
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| Series: | BMC Biology |
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| Online Access: | https://doi.org/10.1186/s12915-021-00953-1 |
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| author | Corentin Affortit François Casas Sabine Ladrech Jean-Charles Ceccato Jérôme Bourien Carolanne Coyat Jean-Luc Puel Marc Lenoir Jing Wang |
| author_facet | Corentin Affortit François Casas Sabine Ladrech Jean-Charles Ceccato Jérôme Bourien Carolanne Coyat Jean-Luc Puel Marc Lenoir Jing Wang |
| author_sort | Corentin Affortit |
| collection | DOAJ |
| description | Abstract Background Age-related hearing loss (ARHL), also known as presbycusis, is the most common sensory impairment seen in elderly people. However, the cochlear aging process does not affect people uniformly, suggesting that both genetic and environmental (e.g., noise, ototoxic drugs) factors and their interaction may influence the onset and severity of ARHL. Considering the potential links between thyroid hormone, mitochondrial activity, and hearing, here, we probed the role of p43, a N-terminally truncated and ligand-binding form of the nuclear receptor TRα1, in hearing function and in the maintenance of hearing during aging in p43−/− mice through complementary approaches, including in vivo electrophysiological recording, ultrastructural assessments, biochemistry, and molecular biology. Results We found that the p43−/− mice exhibit no obvious hearing loss in juvenile stages, but that these mice developed a premature, and more severe, ARHL resulting from the loss of cochlear sensory outer and inner hair cells and degeneration of spiral ganglion neurons. Exacerbated ARHL in p43−/− mice was associated with the early occurrence of a drastic fall of SIRT1 expression, together with an imbalance between pro-apoptotic Bax, p53 expression, and anti-apoptotic Bcl2 expression, as well as an increase in mitochondrial dysfunction, oxidative stress, and inflammatory process. Finally, p43−/− mice were also more vulnerable to noise-induced hearing loss. Conclusions These results demonstrate for the first time a requirement for p43 in the maintenance of hearing during aging and highlight the need to probe the potential link between human THRA gene polymorphisms and/or mutations and accelerated age-related deafness or some adult-onset syndromic deafness. |
| first_indexed | 2024-12-16T15:08:46Z |
| format | Article |
| id | doaj.art-4f5efc551f3b431ea25e66cce3a66370 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-12-16T15:08:46Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-4f5efc551f3b431ea25e66cce3a663702022-12-21T22:27:01ZengBMCBMC Biology1741-70072021-02-0119112010.1186/s12915-021-00953-1Exacerbated age-related hearing loss in mice lacking the p43 mitochondrial T3 receptorCorentin Affortit0François Casas1Sabine Ladrech2Jean-Charles Ceccato3Jérôme Bourien4Carolanne Coyat5Jean-Luc Puel6Marc Lenoir7Jing Wang8INSERM - UMR 1051, Institut des Neurosciences de MontpellierINRA, UMR 866 Dynamique Musculaire et Métabolisme,INSERM - UMR 1051, Institut des Neurosciences de MontpellierINSERM - UMR 1051, Institut des Neurosciences de MontpellierINSERM - UMR 1051, Institut des Neurosciences de MontpellierINSERM - UMR 1051, Institut des Neurosciences de MontpellierINSERM - UMR 1051, Institut des Neurosciences de MontpellierINSERM - UMR 1051, Institut des Neurosciences de MontpellierINSERM - UMR 1051, Institut des Neurosciences de MontpellierAbstract Background Age-related hearing loss (ARHL), also known as presbycusis, is the most common sensory impairment seen in elderly people. However, the cochlear aging process does not affect people uniformly, suggesting that both genetic and environmental (e.g., noise, ototoxic drugs) factors and their interaction may influence the onset and severity of ARHL. Considering the potential links between thyroid hormone, mitochondrial activity, and hearing, here, we probed the role of p43, a N-terminally truncated and ligand-binding form of the nuclear receptor TRα1, in hearing function and in the maintenance of hearing during aging in p43−/− mice through complementary approaches, including in vivo electrophysiological recording, ultrastructural assessments, biochemistry, and molecular biology. Results We found that the p43−/− mice exhibit no obvious hearing loss in juvenile stages, but that these mice developed a premature, and more severe, ARHL resulting from the loss of cochlear sensory outer and inner hair cells and degeneration of spiral ganglion neurons. Exacerbated ARHL in p43−/− mice was associated with the early occurrence of a drastic fall of SIRT1 expression, together with an imbalance between pro-apoptotic Bax, p53 expression, and anti-apoptotic Bcl2 expression, as well as an increase in mitochondrial dysfunction, oxidative stress, and inflammatory process. Finally, p43−/− mice were also more vulnerable to noise-induced hearing loss. Conclusions These results demonstrate for the first time a requirement for p43 in the maintenance of hearing during aging and highlight the need to probe the potential link between human THRA gene polymorphisms and/or mutations and accelerated age-related deafness or some adult-onset syndromic deafness.https://doi.org/10.1186/s12915-021-00953-1Age-related hearing lossThyroid hormonesp43 mitochondrial T3 receptorMitochondrial dysfunction |
| spellingShingle | Corentin Affortit François Casas Sabine Ladrech Jean-Charles Ceccato Jérôme Bourien Carolanne Coyat Jean-Luc Puel Marc Lenoir Jing Wang Exacerbated age-related hearing loss in mice lacking the p43 mitochondrial T3 receptor BMC Biology Age-related hearing loss Thyroid hormones p43 mitochondrial T3 receptor Mitochondrial dysfunction |
| title | Exacerbated age-related hearing loss in mice lacking the p43 mitochondrial T3 receptor |
| title_full | Exacerbated age-related hearing loss in mice lacking the p43 mitochondrial T3 receptor |
| title_fullStr | Exacerbated age-related hearing loss in mice lacking the p43 mitochondrial T3 receptor |
| title_full_unstemmed | Exacerbated age-related hearing loss in mice lacking the p43 mitochondrial T3 receptor |
| title_short | Exacerbated age-related hearing loss in mice lacking the p43 mitochondrial T3 receptor |
| title_sort | exacerbated age related hearing loss in mice lacking the p43 mitochondrial t3 receptor |
| topic | Age-related hearing loss Thyroid hormones p43 mitochondrial T3 receptor Mitochondrial dysfunction |
| url | https://doi.org/10.1186/s12915-021-00953-1 |
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