Protection from noise-induced cochlear synaptopathy by virally mediated overexpression of NT3

Abstract Noise exposures causing only transient threshold shifts can destroy auditory-nerve synapses without damaging hair cells. Here, we asked whether virally mediated neurotrophin3 (NT3) overexpression can repair this damage. CBA/CaJ mice at 6 wks were injected unilaterally with adeno-associated...

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Autores principales:	Ken Hashimoto, Tyler T. Hickman, Jun Suzuki, Lingchao Ji, David C. Kohrman, Gabriel Corfas, M. Charles Liberman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ee0860e21d1648468a10153d8c2a20c3
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spelling	oai:doaj.org-article:ee0860e21d1648468a10153d8c2a20c32021-12-02T16:08:05ZProtection from noise-induced cochlear synaptopathy by virally mediated overexpression of NT310.1038/s41598-019-51724-62045-2322https://doaj.org/article/ee0860e21d1648468a10153d8c2a20c32019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-51724-6https://doaj.org/toc/2045-2322Abstract Noise exposures causing only transient threshold shifts can destroy auditory-nerve synapses without damaging hair cells. Here, we asked whether virally mediated neurotrophin3 (NT3) overexpression can repair this damage. CBA/CaJ mice at 6 wks were injected unilaterally with adeno-associated virus (AAV) containing either NT3 or GFP genes, via the posterior semicircular canal, 3 wks prior to, or 5 hrs after, noise exposure. Controls included exposed animals receiving vehicle only, and unexposed animals receiving virus. Thresholds were measured 2 wks post-exposure, just before cochleas were harvested for histological analysis. In separate virus-injected animals, unexposed cochleas were extracted for qRT-PCR. The GFP reporter showed that inner hair cells (IHCs) were transfected throughout the cochlea, and outer hair cells mainly in the apex. qRT-PCR showed 4- to 10-fold overexpression of NT3 from 1–21 days post-injection, and 1.7-fold overexpression at 40 days. AAV-NT3 delivered prior to noise exposure produced a dose-dependent reduction of synaptopathy, with nearly complete rescue at some cochlear locations. In unexposed ears, NT3 overexpression did not affect thresholds, however GFP overexpression caused IHC loss. In exposed ears, NT3 overexpression increased permanent threshold shifts. Thus, although NT3 overexpression can minimize noise-induced synaptic damage, the forced overexpression may be harmful to hair cells themselves during cochlear overstimulation.Ken HashimotoTyler T. HickmanJun SuzukiLingchao JiDavid C. KohrmanGabriel CorfasM. Charles LibermanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ken Hashimoto Tyler T. Hickman Jun Suzuki Lingchao Ji David C. Kohrman Gabriel Corfas M. Charles Liberman Protection from noise-induced cochlear synaptopathy by virally mediated overexpression of NT3
description	Abstract Noise exposures causing only transient threshold shifts can destroy auditory-nerve synapses without damaging hair cells. Here, we asked whether virally mediated neurotrophin3 (NT3) overexpression can repair this damage. CBA/CaJ mice at 6 wks were injected unilaterally with adeno-associated virus (AAV) containing either NT3 or GFP genes, via the posterior semicircular canal, 3 wks prior to, or 5 hrs after, noise exposure. Controls included exposed animals receiving vehicle only, and unexposed animals receiving virus. Thresholds were measured 2 wks post-exposure, just before cochleas were harvested for histological analysis. In separate virus-injected animals, unexposed cochleas were extracted for qRT-PCR. The GFP reporter showed that inner hair cells (IHCs) were transfected throughout the cochlea, and outer hair cells mainly in the apex. qRT-PCR showed 4- to 10-fold overexpression of NT3 from 1–21 days post-injection, and 1.7-fold overexpression at 40 days. AAV-NT3 delivered prior to noise exposure produced a dose-dependent reduction of synaptopathy, with nearly complete rescue at some cochlear locations. In unexposed ears, NT3 overexpression did not affect thresholds, however GFP overexpression caused IHC loss. In exposed ears, NT3 overexpression increased permanent threshold shifts. Thus, although NT3 overexpression can minimize noise-induced synaptic damage, the forced overexpression may be harmful to hair cells themselves during cochlear overstimulation.
format	article
author	Ken Hashimoto Tyler T. Hickman Jun Suzuki Lingchao Ji David C. Kohrman Gabriel Corfas M. Charles Liberman
author_facet	Ken Hashimoto Tyler T. Hickman Jun Suzuki Lingchao Ji David C. Kohrman Gabriel Corfas M. Charles Liberman
author_sort	Ken Hashimoto
title	Protection from noise-induced cochlear synaptopathy by virally mediated overexpression of NT3
title_short	Protection from noise-induced cochlear synaptopathy by virally mediated overexpression of NT3
title_full	Protection from noise-induced cochlear synaptopathy by virally mediated overexpression of NT3
title_fullStr	Protection from noise-induced cochlear synaptopathy by virally mediated overexpression of NT3
title_full_unstemmed	Protection from noise-induced cochlear synaptopathy by virally mediated overexpression of NT3
title_sort	protection from noise-induced cochlear synaptopathy by virally mediated overexpression of nt3
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/ee0860e21d1648468a10153d8c2a20c3
work_keys_str_mv	AT kenhashimoto protectionfromnoiseinducedcochlearsynaptopathybyvirallymediatedoverexpressionofnt3 AT tylerthickman protectionfromnoiseinducedcochlearsynaptopathybyvirallymediatedoverexpressionofnt3 AT junsuzuki protectionfromnoiseinducedcochlearsynaptopathybyvirallymediatedoverexpressionofnt3 AT lingchaoji protectionfromnoiseinducedcochlearsynaptopathybyvirallymediatedoverexpressionofnt3 AT davidckohrman protectionfromnoiseinducedcochlearsynaptopathybyvirallymediatedoverexpressionofnt3 AT gabrielcorfas protectionfromnoiseinducedcochlearsynaptopathybyvirallymediatedoverexpressionofnt3 AT mcharlesliberman protectionfromnoiseinducedcochlearsynaptopathybyvirallymediatedoverexpressionofnt3
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Protection from noise-induced cochlear synaptopathy by virally mediated overexpression of NT3

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