{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:45:31Z","timestamp":1790034331676,"version":"4.0.1"},"reference-count":83,"publisher":"Wiley","license":[{"start":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T00:00:00Z","timestamp":1601856000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Incubation Foundation of Xi\u2019an People\u2019s Hospital\/Xi\u2019an Fourth Hospital","award":["ZD-3"],"award-info":[{"award-number":["ZD-3"]}]},{"name":"Scientific Incubation Foundation of Xi\u2019an People\u2019s Hospital\/Xi\u2019an Fourth Hospital","award":["14QNP023"],"award-info":[{"award-number":["14QNP023"]}]},{"name":"Scientific Incubation Foundation of Xi\u2019an People\u2019s Hospital\/Xi\u2019an Fourth Hospital","award":["81803187"],"award-info":[{"award-number":["81803187"]}]},{"name":"Scientific Incubation Foundation of Xi\u2019an People\u2019s Hospital\/Xi\u2019an Fourth Hospital","award":["81172635"],"award-info":[{"award-number":["81172635"]}]},{"name":"Scientific Incubation Foundation of Xi\u2019an People\u2019s Hospital\/Xi\u2019an Fourth Hospital","award":["81400459"],"award-info":[{"award-number":["81400459"]}]},{"name":"Scientific Incubation Foundation of Xi\u2019an People\u2019s Hospital\/Xi\u2019an Fourth Hospital","award":["81110097"],"award-info":[{"award-number":["81110097"]}]},{"name":"Military Medical Science and Technology","award":["ZD-3"],"award-info":[{"award-number":["ZD-3"]}]},{"name":"Military Medical Science and Technology","award":["14QNP023"],"award-info":[{"award-number":["14QNP023"]}]},{"name":"Military Medical Science and Technology","award":["81803187"],"award-info":[{"award-number":["81803187"]}]},{"name":"Military Medical Science and Technology","award":["81172635"],"award-info":[{"award-number":["81172635"]}]},{"name":"Military Medical Science and Technology","award":["81400459"],"award-info":[{"award-number":["81400459"]}]},{"name":"Military Medical Science and Technology","award":["81110097"],"award-info":[{"award-number":["81110097"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["ZD-3"],"award-info":[{"award-number":["ZD-3"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["14QNP023"],"award-info":[{"award-number":["14QNP023"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803187"],"award-info":[{"award-number":["81803187"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81172635"],"award-info":[{"award-number":["81172635"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81400459"],"award-info":[{"award-number":["81400459"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81110097"],"award-info":[{"award-number":["81110097"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neural Plasticity"],"published-print":{"date-parts":[[2020,10,5]]},"abstract":"<jats:p>Sound conditioning (SC) is defined as \u201ctoughening\u201d to lower levels of sound over time, which reduces a subsequent noise-induced threshold shift. Although the protective effect of SC in mammals is generally understood, the exact mechanisms involved have not yet been elucidated. To confirm the protective effect of SC against noise exposure (NE) and the stress-related signaling pathway of its rescue, we observed target molecule changes caused by SC of low frequency prior to NE as well as histology analysis in vivo and verified the suggested mechanisms in SGNs in vitro. Further, we investigated the potential role of Hsp70 and Bmi1 in SC by targeting SOD1 and SOD2 which are regulated by the FoxO1 signaling pathway based on mitochondrial function and reactive oxygen species (ROS) levels. Finally, we sought to identify the possible molecular mechanisms associated with the beneficial effects of SC against noise-induced trauma. Data from the rat model were evaluated by western blot, immunofluorescence, and RT-PCR. The results revealed that SC upregulated Hsp70, Bmi1, FoxO1, SOD1, and SOD2 expression in spiral ganglion neurons (SGNs). Moreover, the auditory brainstem responses (ABRs) and electron microscopy revealed that SC could protect against acute acoustic trauma (AAT) based on a significant reduction of hearing impairment and visible reduction in outer hair cell loss as well as ultrastructural changes in OHCs and SGNs. Collectively, these results suggested that the contribution of Bmi1 toward decreased sensitivity to noise-induced trauma following SC was triggered by Hsp70 induction and associated with enhancement of the antioxidant system and decreased mitochondrial superoxide accumulation. This contribution of Bmi1 was achieved by direct targeting of SOD1 and SOD2, which was regulated by FoxO1. Therefore, the Hsp70\/Bmi1-FoxO1-SOD signaling pathway might contribute to the protective effect of SC against AAT in a rat model.<\/jats:p>","DOI":"10.1155\/2020\/8823785","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T19:20:07Z","timestamp":1601925607000},"page":"1-22","source":"Crossref","is-referenced-by-count":13,"title":["Hsp70\/Bmi1-FoxO1-SOD Signaling Pathway Contributes to the Protective Effect of Sound Conditioning against Acute Acoustic Trauma in a Rat Model"],"prefix":"10.1155","volume":"2020","author":[{"given":"Guoxia","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi, 710032, China"},{"name":"Department of Otolaryngology, Head and Neck Surgery, Xi\u2019an People\u2019s Hospital\/Xi\u2019an Fourth Hospital, Xi\u2019an, Shaanxi, 710043, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi, 710032, China"},{"name":"Department of Otolaryngology-Head and Neck Surgery, Chinese PLA General Hospital, Beijing, 100853, China"},{"name":"Department of Otolaryngology-Head and Neck Surgery, General Hospital of Xinjiang Military Region, Urumchi, Xinjiang, 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi, 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1646-3232","authenticated-orcid":true,"given":"Keyong","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi, 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Mi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi, 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinqin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment and Shaanxi Key Laboratory of Free Radical Biology and Medicine, Fourth Military Medical University, Xi\u2019an, Shaanxi, 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, General Hospital of Xinjiang Military Region, Urumchi, Xinjiang, 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwen","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, The Fifth Affiliated Hospital of Xinjing Medical University, Urumchi, Xinjiang, 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7296-7849","authenticated-orcid":true,"given":"Jiasheng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, Xi\u2019an People\u2019s Hospital\/Xi\u2019an Fourth Hospital, Xi\u2019an, Shaanxi, 710043, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1460-1961","authenticated-orcid":true,"given":"Lianjun","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Tangdu Hospital, Fourth Military Medical University, Xi\u2019an, 710038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4185-100X","authenticated-orcid":true,"given":"Jianhua","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi, 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(92)90017-H"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.3109\/00016489709124081"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(97)00214-1"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(02)00646-9"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1539\/joh.L8032"},{"key":"6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fnana.2016.00019","article-title":"Noise-induced \"toughening\" effect in Wistar rats: enhanced auditory brainstem responses are related to calretinin and nitric oxide synthase upregulation","volume":"10","author":"J. C. Alvarado","year":"2016","journal-title":"Frontiers in Neuroanatomy"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71353"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjorl.2019.01.003"},{"issue":"3","key":"9","first-page":"2852","article-title":"Identification of functional tag single nucleotide polmorphisms within the entire CAT gene and their clinical relevance in patients with noise-induced hearing loss","volume":"8","author":"J. Yang","year":"2015","journal-title":"International Journal of Clinical and Experimental Pathology"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00060"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1155\/2009\/908596"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(96)00126-8"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(00)00036-8"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(01)00224-6"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.03.141"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101364"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7288"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.35"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgt111"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.549"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-9686-8"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026728"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-014-0136-0"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2013.10.002"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(91)90041-7"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0123130"},{"issue":"10","key":"27","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1179\/1743132812Y.0000000098","article-title":"Intranuclear localization of apoptosis-inducing factor and endonuclease G involves in peroxynitrite-induced apoptosis of spiral ganglion neurons","volume":"34","author":"W. Liu","year":"2012","journal-title":"Neurological Research"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.3626"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00362"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00401"},{"issue":"1","key":"31","first-page":"130","article-title":"Espin distribution as revealed by super-resolution microscopy of stereocilia","volume":"12","author":"J. Qi","year":"2020","journal-title":"American Journal of Translational Research"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-018-0076-4"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00590"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2019.00264"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00139"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2017.1359449"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.10.021"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03291-2"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1437-0"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00137"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00426"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00241"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2019.06.054"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2019.00190"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2019.00436"},{"issue":"6","key":"46","first-page":"3246","article-title":"The application of graphene-based biomaterials in biomedicine","volume":"11","author":"S. Han","year":"2019","journal-title":"American Journal of Translational Research"},{"key":"47","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-017-0471-0"},{"key":"48","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4280407"},{"key":"49","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2020.112073"},{"key":"50","doi-asserted-by":"publisher","DOI":"10.1242\/dev.103036"},{"key":"51","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00147"},{"key":"52","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00213"},{"key":"53","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00122"},{"key":"54","doi-asserted-by":"publisher","DOI":"10.1038\/srep29418"},{"key":"55","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7613"},{"key":"56","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200209000-00001"},{"key":"57","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(95)00020-5"},{"key":"58","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(94)90038-8"},{"key":"59","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(00)00161-1"},{"key":"60","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903503106"},{"key":"61","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.16.7290"},{"key":"62","doi-asserted-by":"publisher","DOI":"10.1038\/346623a0"},{"key":"63","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5268.1606"},{"key":"64","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-006-0043-x"},{"key":"65","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2011.76"},{"key":"66","doi-asserted-by":"publisher","DOI":"10.1172\/JCI68480"},{"key":"67","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-008-0122-2"},{"key":"68","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-008-0097-2"},{"key":"69","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2010.12.014"},{"key":"70","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2018.02.006"},{"key":"71","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2011.06.003"},{"key":"72","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.09.004"},{"key":"73","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-22-10116.1999"},{"key":"74","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.11.032"},{"key":"75","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031870"},{"key":"76","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5303-08.2009"},{"key":"77","doi-asserted-by":"publisher","DOI":"10.1038\/nature08040"},{"key":"78","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-209734"},{"key":"79","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036209"},{"key":"80","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.11"},{"key":"81","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2015.06.019"},{"key":"82","doi-asserted-by":"publisher","DOI":"10.1159\/000487576"},{"key":"83","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00278"}],"container-title":["Neural Plasticity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/np\/2020\/8823785.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/np\/2020\/8823785.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/np\/2020\/8823785.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T03:57:17Z","timestamp":1605499037000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/np\/2020\/8823785\/"}},"subtitle":[],"editor":[{"given":"Renjie","family":"Chai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,10,5]]},"references-count":83,"alternative-id":["8823785","8823785"],"URL":"https:\/\/doi.org\/10.1155\/2020\/8823785","relation":{},"ISSN":["1687-5443","2090-5904"],"issn-type":[{"value":"1687-5443","type":"electronic"},{"value":"2090-5904","type":"print"}],"subject":[],"published":{"date-parts":[[2020,10,5]]}}}