Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure

Abstract Noise induced hearing loss (NIHL) is a disease that affects millions of Americans. Identifying genetic pathways that influence recovery from noise exposure is an important step forward in understanding NIHL. The transcription factor Foxo3 integrates the cellular response to oxidative stress...

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Autores principales:	Felicia Gilels, Stephen T. Paquette, Holly J. Beaulac, Anwen Bullen, Patricia M. White
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/73b48b44d0244223aa65432907473c86
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spelling	oai:doaj.org-article:73b48b44d0244223aa65432907473c862021-12-02T12:30:54ZSevere hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure10.1038/s41598-017-01142-32045-2322https://doaj.org/article/73b48b44d0244223aa65432907473c862017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01142-3https://doaj.org/toc/2045-2322Abstract Noise induced hearing loss (NIHL) is a disease that affects millions of Americans. Identifying genetic pathways that influence recovery from noise exposure is an important step forward in understanding NIHL. The transcription factor Foxo3 integrates the cellular response to oxidative stress and plays a role in extending lifespan in many organisms, including humans. Here we show that Foxo3 is required for auditory function after noise exposure in a mouse model system, measured by ABR. Absent Foxo3, outer hair cells are lost throughout the middle and higher frequencies. SEM reveals persistent damage to some surviving outer hair cell stereocilia. However, DPOAE analysis reveals that some function is preserved in low frequency outer hair cells, despite concomitant profound hearing loss. Inner hair cells, auditory synapses and spiral ganglion neurons are all present after noise exposure in the Foxo3KO/KO fourteen days post noise (DPN). We also report anti-Foxo3 immunofluorescence in adult human outer hair cells. Taken together, these data implicate Foxo3 and its transcriptional targets in outer hair cell survival after noise damage. An additional role for Foxo3 in preserving hearing is likely, as low frequency auditory function is absent in noise exposed Foxo3KO/KOs even though all cells and structures are present.Felicia GilelsStephen T. PaquetteHolly J. BeaulacAnwen BullenPatricia M. WhiteNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Felicia Gilels Stephen T. Paquette Holly J. Beaulac Anwen Bullen Patricia M. White Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure
description	Abstract Noise induced hearing loss (NIHL) is a disease that affects millions of Americans. Identifying genetic pathways that influence recovery from noise exposure is an important step forward in understanding NIHL. The transcription factor Foxo3 integrates the cellular response to oxidative stress and plays a role in extending lifespan in many organisms, including humans. Here we show that Foxo3 is required for auditory function after noise exposure in a mouse model system, measured by ABR. Absent Foxo3, outer hair cells are lost throughout the middle and higher frequencies. SEM reveals persistent damage to some surviving outer hair cell stereocilia. However, DPOAE analysis reveals that some function is preserved in low frequency outer hair cells, despite concomitant profound hearing loss. Inner hair cells, auditory synapses and spiral ganglion neurons are all present after noise exposure in the Foxo3KO/KO fourteen days post noise (DPN). We also report anti-Foxo3 immunofluorescence in adult human outer hair cells. Taken together, these data implicate Foxo3 and its transcriptional targets in outer hair cell survival after noise damage. An additional role for Foxo3 in preserving hearing is likely, as low frequency auditory function is absent in noise exposed Foxo3KO/KOs even though all cells and structures are present.
format	article
author	Felicia Gilels Stephen T. Paquette Holly J. Beaulac Anwen Bullen Patricia M. White
author_facet	Felicia Gilels Stephen T. Paquette Holly J. Beaulac Anwen Bullen Patricia M. White
author_sort	Felicia Gilels
title	Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure
title_short	Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure
title_full	Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure
title_fullStr	Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure
title_full_unstemmed	Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure
title_sort	severe hearing loss and outer hair cell death in homozygous foxo3 knockout mice after moderate noise exposure
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/73b48b44d0244223aa65432907473c86
work_keys_str_mv	AT feliciagilels severehearinglossandouterhaircelldeathinhomozygousfoxo3knockoutmiceaftermoderatenoiseexposure AT stephentpaquette severehearinglossandouterhaircelldeathinhomozygousfoxo3knockoutmiceaftermoderatenoiseexposure AT hollyjbeaulac severehearinglossandouterhaircelldeathinhomozygousfoxo3knockoutmiceaftermoderatenoiseexposure AT anwenbullen severehearinglossandouterhaircelldeathinhomozygousfoxo3knockoutmiceaftermoderatenoiseexposure AT patriciamwhite severehearinglossandouterhaircelldeathinhomozygousfoxo3knockoutmiceaftermoderatenoiseexposure
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Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure

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