Differences in Calcium Clearance at Inner Hair Cell Active Zones May Underlie the Difference in Susceptibility to Noise-Induced Cochlea Synaptopathy of C57BL/6J and CBA/CaJ Mice
Noise exposure of a short period at a moderate level can produce permanent cochlear synaptopathy without seeing lasting changes in audiometric threshold. However, due to the species differences in inner hair cell (IHC) calcium current that we have recently discovered, the susceptibility to noise exp...
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Frontiers Media S.A.
2021-02-01
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Series: | Frontiers in Cell and Developmental Biology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2020.635201/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hongchao Liu Hongchao Liu Hongchao Liu Hu Peng Longhao Wang Longhao Wang Longhao Wang Pengcheng Xu Pengcheng Xu Pengcheng Xu Zhaoyan Wang Zhaoyan Wang Zhaoyan Wang Huihui Liu Huihui Liu Huihui Liu Hao Wu Hao Wu Hao Wu |
spellingShingle |
Hongchao Liu Hongchao Liu Hongchao Liu Hu Peng Longhao Wang Longhao Wang Longhao Wang Pengcheng Xu Pengcheng Xu Pengcheng Xu Zhaoyan Wang Zhaoyan Wang Zhaoyan Wang Huihui Liu Huihui Liu Huihui Liu Hao Wu Hao Wu Hao Wu Differences in Calcium Clearance at Inner Hair Cell Active Zones May Underlie the Difference in Susceptibility to Noise-Induced Cochlea Synaptopathy of C57BL/6J and CBA/CaJ Mice Frontiers in Cell and Developmental Biology noise-induced cochlear synaptopathy calcium clearance mitochondrial inner hair cell presynaptic ribbon |
author_facet |
Hongchao Liu Hongchao Liu Hongchao Liu Hu Peng Longhao Wang Longhao Wang Longhao Wang Pengcheng Xu Pengcheng Xu Pengcheng Xu Zhaoyan Wang Zhaoyan Wang Zhaoyan Wang Huihui Liu Huihui Liu Huihui Liu Hao Wu Hao Wu Hao Wu |
author_sort |
Hongchao Liu |
title |
Differences in Calcium Clearance at Inner Hair Cell Active Zones May Underlie the Difference in Susceptibility to Noise-Induced Cochlea Synaptopathy of C57BL/6J and CBA/CaJ Mice |
title_short |
Differences in Calcium Clearance at Inner Hair Cell Active Zones May Underlie the Difference in Susceptibility to Noise-Induced Cochlea Synaptopathy of C57BL/6J and CBA/CaJ Mice |
title_full |
Differences in Calcium Clearance at Inner Hair Cell Active Zones May Underlie the Difference in Susceptibility to Noise-Induced Cochlea Synaptopathy of C57BL/6J and CBA/CaJ Mice |
title_fullStr |
Differences in Calcium Clearance at Inner Hair Cell Active Zones May Underlie the Difference in Susceptibility to Noise-Induced Cochlea Synaptopathy of C57BL/6J and CBA/CaJ Mice |
title_full_unstemmed |
Differences in Calcium Clearance at Inner Hair Cell Active Zones May Underlie the Difference in Susceptibility to Noise-Induced Cochlea Synaptopathy of C57BL/6J and CBA/CaJ Mice |
title_sort |
differences in calcium clearance at inner hair cell active zones may underlie the difference in susceptibility to noise-induced cochlea synaptopathy of c57bl/6j and cba/caj mice |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-02-01 |
description |
Noise exposure of a short period at a moderate level can produce permanent cochlear synaptopathy without seeing lasting changes in audiometric threshold. However, due to the species differences in inner hair cell (IHC) calcium current that we have recently discovered, the susceptibility to noise exposure may vary, thereby impact outcomes of noise exposure. In this study, we investigate the consequences of noise exposure in the two commonly used animal models in hearing research, CBA/CaJ (CBA) and C57BL/6J (B6) mice, focusing on the functional changes of cochlear IHCs. In the CBA mice, moderate noise exposure resulted in a typical fully recovered audiometric threshold but a reduced wave I amplitude of auditory brainstem responses. In contrast, both auditory brainstem response threshold and wave I amplitude fully recovered in B6 mice at 2 weeks after noise exposure. Confocal microscopy observations found that ribbon synapses of IHCs recovered in B6 mice but not in CBA mice. To further characterize the molecular mechanism underlying these different phenotypes in synaptopathy, we compared the ratio of Bax/Bcl-2 with the expression of cytochrome-C and found increased activity in CBA mice after noise exposure. Under whole-cell patch clamped IHCs, we acquired two-photon calcium imaging around the active zone to evaluate the Ca2+ clearance rate and found that CBA mice have a slower calcium clearance rate. Our results indicated that excessive accumulation of calcium due to acoustic overexposure and slow clearance around the presynaptic ribbon might lead to disruption of calcium homeostasis, followed by mitochondrial dysfunction of IHCs that cause susceptibility of noise-induced cochlear synaptopathy in CBA mice. |
topic |
noise-induced cochlear synaptopathy calcium clearance mitochondrial inner hair cell presynaptic ribbon |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2020.635201/full |
work_keys_str_mv |
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doaj-4424bc2478654629ab763aae5c16b2c22021-02-05T06:26:04ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-02-01810.3389/fcell.2020.635201635201Differences in Calcium Clearance at Inner Hair Cell Active Zones May Underlie the Difference in Susceptibility to Noise-Induced Cochlea Synaptopathy of C57BL/6J and CBA/CaJ MiceHongchao Liu0Hongchao Liu1Hongchao Liu2Hu Peng3Longhao Wang4Longhao Wang5Longhao Wang6Pengcheng Xu7Pengcheng Xu8Pengcheng Xu9Zhaoyan Wang10Zhaoyan Wang11Zhaoyan Wang12Huihui Liu13Huihui Liu14Huihui Liu15Hao Wu16Hao Wu17Hao Wu18Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaEar Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaEar Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaEar Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaEar Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaEar Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaEar Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, ChinaNoise exposure of a short period at a moderate level can produce permanent cochlear synaptopathy without seeing lasting changes in audiometric threshold. However, due to the species differences in inner hair cell (IHC) calcium current that we have recently discovered, the susceptibility to noise exposure may vary, thereby impact outcomes of noise exposure. In this study, we investigate the consequences of noise exposure in the two commonly used animal models in hearing research, CBA/CaJ (CBA) and C57BL/6J (B6) mice, focusing on the functional changes of cochlear IHCs. In the CBA mice, moderate noise exposure resulted in a typical fully recovered audiometric threshold but a reduced wave I amplitude of auditory brainstem responses. In contrast, both auditory brainstem response threshold and wave I amplitude fully recovered in B6 mice at 2 weeks after noise exposure. Confocal microscopy observations found that ribbon synapses of IHCs recovered in B6 mice but not in CBA mice. To further characterize the molecular mechanism underlying these different phenotypes in synaptopathy, we compared the ratio of Bax/Bcl-2 with the expression of cytochrome-C and found increased activity in CBA mice after noise exposure. Under whole-cell patch clamped IHCs, we acquired two-photon calcium imaging around the active zone to evaluate the Ca2+ clearance rate and found that CBA mice have a slower calcium clearance rate. Our results indicated that excessive accumulation of calcium due to acoustic overexposure and slow clearance around the presynaptic ribbon might lead to disruption of calcium homeostasis, followed by mitochondrial dysfunction of IHCs that cause susceptibility of noise-induced cochlear synaptopathy in CBA mice.https://www.frontiersin.org/articles/10.3389/fcell.2020.635201/fullnoise-induced cochlear synaptopathycalcium clearancemitochondrialinner hair cellpresynaptic ribbon |