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Efr3a Insufficiency Attenuates the Degeneration of Spiral Ganglion Neurons after Hair Cell Loss

Sensorineural hearing loss (SNHL) is caused by an irreversible impairment of cochlear hair cells and subsequent progressive degeneration of spiral ganglion neurons (SGNs). Eighty-five requiring 3 (Efr3) is a plasma membrane protein conserved from yeast to human, and knockout of Efr3a was reported to...

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Autores principales: Hu, Haixia, Ye, Bin, Zhang, Le, Wang, Quan, Liu, Zhiwei, Ji, Suying, Liu, Qiuju, Lv, Jingrong, Ma, Yan, Xu, Ying, Wu, Hao, Huang, Fude, Xiang, Mingliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372784/
https://www.ncbi.nlm.nih.gov/pubmed/28424585
http://dx.doi.org/10.3389/fnmol.2017.00086
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author Hu, Haixia
Ye, Bin
Zhang, Le
Wang, Quan
Liu, Zhiwei
Ji, Suying
Liu, Qiuju
Lv, Jingrong
Ma, Yan
Xu, Ying
Wu, Hao
Huang, Fude
Xiang, Mingliang
author_facet Hu, Haixia
Ye, Bin
Zhang, Le
Wang, Quan
Liu, Zhiwei
Ji, Suying
Liu, Qiuju
Lv, Jingrong
Ma, Yan
Xu, Ying
Wu, Hao
Huang, Fude
Xiang, Mingliang
author_sort Hu, Haixia
collection PubMed
description Sensorineural hearing loss (SNHL) is caused by an irreversible impairment of cochlear hair cells and subsequent progressive degeneration of spiral ganglion neurons (SGNs). Eighty-five requiring 3 (Efr3) is a plasma membrane protein conserved from yeast to human, and knockout of Efr3a was reported to facilitate the survival of hippocampal newborn neurons in adult mice. Previously, we found Efr3a expression in the auditory neural pathway is upregulated soon after the destruction of hair cells. Here we conducted a time-course analysis of drug-caused damage to hearing ability, hair cells and SGNs in Efr3a knocking down mice (Efr3a(−/+), Efr3a KD) and their wild type littermates. Functional examination showed that both groups of mice suffered from serious hearing loss with a higher level of severity in wild type (WT) mice. Morphologic observation following drugs administration showed that both WT and Efr3a KD mice went through progressive loss of hair cells and SGNs, in association with degenerative changes in the perikarya, intracellular organelles, cell body conformation in SGNs, and the changes of SGNs in WT mice were more severe than in Efr3a KD mice. These beneficial effects of Efr3a KD could be ascribed to an increase in the expression of some neurotrophic factors and their receptors in Efr3a KD mice. Our results indicate that Efr3a insufficiency suppresses drug-caused SNHL neurodegeneration in association with an increase in the expression of some neurotrophic factors and their receptors, which may be targeted in the treatment of neurodegeneration.
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spelling pubmed-53727842017-04-19 Efr3a Insufficiency Attenuates the Degeneration of Spiral Ganglion Neurons after Hair Cell Loss Hu, Haixia Ye, Bin Zhang, Le Wang, Quan Liu, Zhiwei Ji, Suying Liu, Qiuju Lv, Jingrong Ma, Yan Xu, Ying Wu, Hao Huang, Fude Xiang, Mingliang Front Mol Neurosci Neuroscience Sensorineural hearing loss (SNHL) is caused by an irreversible impairment of cochlear hair cells and subsequent progressive degeneration of spiral ganglion neurons (SGNs). Eighty-five requiring 3 (Efr3) is a plasma membrane protein conserved from yeast to human, and knockout of Efr3a was reported to facilitate the survival of hippocampal newborn neurons in adult mice. Previously, we found Efr3a expression in the auditory neural pathway is upregulated soon after the destruction of hair cells. Here we conducted a time-course analysis of drug-caused damage to hearing ability, hair cells and SGNs in Efr3a knocking down mice (Efr3a(−/+), Efr3a KD) and their wild type littermates. Functional examination showed that both groups of mice suffered from serious hearing loss with a higher level of severity in wild type (WT) mice. Morphologic observation following drugs administration showed that both WT and Efr3a KD mice went through progressive loss of hair cells and SGNs, in association with degenerative changes in the perikarya, intracellular organelles, cell body conformation in SGNs, and the changes of SGNs in WT mice were more severe than in Efr3a KD mice. These beneficial effects of Efr3a KD could be ascribed to an increase in the expression of some neurotrophic factors and their receptors in Efr3a KD mice. Our results indicate that Efr3a insufficiency suppresses drug-caused SNHL neurodegeneration in association with an increase in the expression of some neurotrophic factors and their receptors, which may be targeted in the treatment of neurodegeneration. Frontiers Media S.A. 2017-03-29 /pmc/articles/PMC5372784/ /pubmed/28424585 http://dx.doi.org/10.3389/fnmol.2017.00086 Text en Copyright © 2017 Hu, Ye, Zhang, Wang, Liu, Ji, Liu, Lv, Ma, Xu, Wu, Huang and Xiang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Hu, Haixia
Ye, Bin
Zhang, Le
Wang, Quan
Liu, Zhiwei
Ji, Suying
Liu, Qiuju
Lv, Jingrong
Ma, Yan
Xu, Ying
Wu, Hao
Huang, Fude
Xiang, Mingliang
Efr3a Insufficiency Attenuates the Degeneration of Spiral Ganglion Neurons after Hair Cell Loss
title Efr3a Insufficiency Attenuates the Degeneration of Spiral Ganglion Neurons after Hair Cell Loss
title_full Efr3a Insufficiency Attenuates the Degeneration of Spiral Ganglion Neurons after Hair Cell Loss
title_fullStr Efr3a Insufficiency Attenuates the Degeneration of Spiral Ganglion Neurons after Hair Cell Loss
title_full_unstemmed Efr3a Insufficiency Attenuates the Degeneration of Spiral Ganglion Neurons after Hair Cell Loss
title_short Efr3a Insufficiency Attenuates the Degeneration of Spiral Ganglion Neurons after Hair Cell Loss
title_sort efr3a insufficiency attenuates the degeneration of spiral ganglion neurons after hair cell loss
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372784/
https://www.ncbi.nlm.nih.gov/pubmed/28424585
http://dx.doi.org/10.3389/fnmol.2017.00086
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