Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice

Recent studies have identified sex-differences in auditory physiology and in the susceptibility to noise-induced hearing loss (NIHL). We hypothesize that 17β-estradiol (E<sub>2</sub>), a known modulator of auditory physiology, may underpin sex-differences in the response to noise trauma....

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Autores principales:	Benjamin Shuster, Ryan Casserly, Erika Lipford, Rafal Olszewski, Béatrice Milon, Shaun Viechweg, Kanisa Davidson, Jennifer Enoch, Mark McMurray, Mark A. Rutherford, Kevin K. Ohlemiller, Michael Hoa, Didier A. Depireux, Jessica A. Mong, Ronna Hertzano
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	noise-induced hearing loss mouse model estrogen sex-differences cochlear synaptopathy inner ear Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/07857183cb4948a9bb8483d0d3ba3a7e
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spelling	oai:doaj.org-article:07857183cb4948a9bb8483d0d3ba3a7e2021-11-25T17:54:21ZEstradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice10.3390/ijms2222122081422-00671661-6596https://doaj.org/article/07857183cb4948a9bb8483d0d3ba3a7e2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12208https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Recent studies have identified sex-differences in auditory physiology and in the susceptibility to noise-induced hearing loss (NIHL). We hypothesize that 17β-estradiol (E<sub>2</sub>), a known modulator of auditory physiology, may underpin sex-differences in the response to noise trauma. Here, we gonadectomized B6CBAF1/J mice and used a combination of electrophysiological and histological techniques to study the effects of estrogen replacement on peripheral auditory physiology in the absence of noise exposure and on protection from NIHL. Functional analysis of auditory physiology in gonadectomized female mice revealed that E<sub>2</sub>-treatment modulated the peripheral response to sound in the absence of changes to the endocochlear potential compared to vehicle-treatment. E<sub>2</sub>-replacement in gonadectomized female mice protected against hearing loss following permanent threshold shift (PTS)- and temporary threshold shift (TTS)-inducing noise exposures. Histological analysis of the cochlear tissue revealed that E<sub>2</sub>-replacement mitigated outer hair cell loss and cochlear synaptopathy following noise exposure compared to vehicle-treatment. Lastly, using fluorescent in situ hybridization, we demonstrate co-localization of estrogen receptor-2 with type-1C, high threshold spiral ganglion neurons, suggesting that the observed protection from cochlear synaptopathy may occur through E<sub>2</sub>-mediated preservation of these neurons. Taken together, these data indicate the estrogen signaling pathways may be harnessed for the prevention and treatment of NIHL.Benjamin ShusterRyan CasserlyErika LipfordRafal OlszewskiBéatrice MilonShaun ViechwegKanisa DavidsonJennifer EnochMark McMurrayMark A. RutherfordKevin K. OhlemillerMichael HoaDidier A. DepireuxJessica A. MongRonna HertzanoMDPI AGarticlenoise-induced hearing lossmouse modelestrogensex-differencescochlear synaptopathyinner earBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12208, p 12208 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	noise-induced hearing loss mouse model estrogen sex-differences cochlear synaptopathy inner ear Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	noise-induced hearing loss mouse model estrogen sex-differences cochlear synaptopathy inner ear Biology (General) QH301-705.5 Chemistry QD1-999 Benjamin Shuster Ryan Casserly Erika Lipford Rafal Olszewski Béatrice Milon Shaun Viechweg Kanisa Davidson Jennifer Enoch Mark McMurray Mark A. Rutherford Kevin K. Ohlemiller Michael Hoa Didier A. Depireux Jessica A. Mong Ronna Hertzano Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice
description	Recent studies have identified sex-differences in auditory physiology and in the susceptibility to noise-induced hearing loss (NIHL). We hypothesize that 17β-estradiol (E<sub>2</sub>), a known modulator of auditory physiology, may underpin sex-differences in the response to noise trauma. Here, we gonadectomized B6CBAF1/J mice and used a combination of electrophysiological and histological techniques to study the effects of estrogen replacement on peripheral auditory physiology in the absence of noise exposure and on protection from NIHL. Functional analysis of auditory physiology in gonadectomized female mice revealed that E<sub>2</sub>-treatment modulated the peripheral response to sound in the absence of changes to the endocochlear potential compared to vehicle-treatment. E<sub>2</sub>-replacement in gonadectomized female mice protected against hearing loss following permanent threshold shift (PTS)- and temporary threshold shift (TTS)-inducing noise exposures. Histological analysis of the cochlear tissue revealed that E<sub>2</sub>-replacement mitigated outer hair cell loss and cochlear synaptopathy following noise exposure compared to vehicle-treatment. Lastly, using fluorescent in situ hybridization, we demonstrate co-localization of estrogen receptor-2 with type-1C, high threshold spiral ganglion neurons, suggesting that the observed protection from cochlear synaptopathy may occur through E<sub>2</sub>-mediated preservation of these neurons. Taken together, these data indicate the estrogen signaling pathways may be harnessed for the prevention and treatment of NIHL.
format	article
author	Benjamin Shuster Ryan Casserly Erika Lipford Rafal Olszewski Béatrice Milon Shaun Viechweg Kanisa Davidson Jennifer Enoch Mark McMurray Mark A. Rutherford Kevin K. Ohlemiller Michael Hoa Didier A. Depireux Jessica A. Mong Ronna Hertzano
author_facet	Benjamin Shuster Ryan Casserly Erika Lipford Rafal Olszewski Béatrice Milon Shaun Viechweg Kanisa Davidson Jennifer Enoch Mark McMurray Mark A. Rutherford Kevin K. Ohlemiller Michael Hoa Didier A. Depireux Jessica A. Mong Ronna Hertzano
author_sort	Benjamin Shuster
title	Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice
title_short	Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice
title_full	Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice
title_fullStr	Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice
title_full_unstemmed	Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice
title_sort	estradiol protects against noise-induced hearing loss and modulates auditory physiology in female mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/07857183cb4948a9bb8483d0d3ba3a7e
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Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice

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