Exacerbated age-related hearing loss in mice lacking the p43 mitochondrial T3 receptor

Autor: Affortit, Corentin, Casas, François, Ladrech, Sabine, Ceccato, Jean-Charles, Bourien, Jérôme, Coyat, Carolanne, Puel, Jean-Luc, Lenoir, Marc, Wang, Jing
Přispěvatelé: Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Dynamique Musculaire et Métabolisme (DMEM), Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neurobiologie de l'audition-plasticité synaptique, Institut National de la Santé et de la Recherche Médicale (INSERM), China Agriculture University [Beijing], Fondation de l'Avenir Et2-675, Fondation Gueules Cassees 77-2017, ANR-10-LABX-0012,EpiGenMed,From Genome and Epigenome to Molecular Medicine: turning new paradigms in biology into the therapeutic strategies of tomorrow(2010), Institut des Neurosciences de Montpellier (INM), Raynaud, Christelle, Laboratoires d'excellence - From Genome and Epigenome to Molecular Medicine: turning new paradigms in biology into the therapeutic strategies of tomorrow - - EpiGenMed2010 - ANR-10-LABX-0012 - LABX - VALID
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: BMC Biology, Vol 19, Iss 1, Pp 1-20 (2021)
BMC Biology
BMC Biology, BioMed Central, 2021, 19 (1), ⟨10.1186/s12915-021-00953-1⟩
ISSN: 1741-7007
DOI: 10.1186/s12915-021-00953-1⟩
Popis: 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. Supplementary Information The online version contains supplementary material available at 10.1186/s12915-021-00953-1.
Databáze: OpenAIRE
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