{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T03:10:09Z","timestamp":1768014609419,"version":"3.49.0"},"reference-count":40,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007660","name":"University of Antwerp","doi-asserted-by":"publisher","award":["BOF DOCPRO Project ID 36959"],"award-info":[{"award-number":["BOF DOCPRO Project ID 36959"]}],"id":[{"id":"10.13039\/501100007660","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Several studies have shown that type IV fibrocytes, located in the spiral ligament, degenerate first after noise exposure. Interestingly, this is the region where Coch expression is most abundant. As it is suggested that cochlin plays a role in our innate immune system, our goal is to investigate hearing thresholds and inner ear inflammation after noise exposure in Coch knockout (Coch\u2212\/\u2212) mice compared to Coch wildtype (Coch+\/+) mice. Animals were randomly allocated to a noise exposure group and a control group. Vestibular and auditory testing was performed at 48 h and one week after noise exposure. Whole mount staining and cryosectioning of the cochlea was performed in order to investigate hair cells, spiral ganglion neurons, inner ear inflammation, Coch expression and fibrocyte degeneration. Hearing assessment revealed that Coch+\/+ mice had significantly larger threshold shifts than Coch\u2212\/\u2212 mice after noise exposure. We were unable to identify any differences in hair cells, neurons, fibrocytes and influx of macrophages in the inner ear between both groups. Interestingly, Coch expression was significantly lower in the group exposed to noise. Our results indicate that the absence of Coch has a protective influence on hearing thresholds after noise exposure, but this is not related to reduced inner ear inflammation in the knockout.<\/jats:p>","DOI":"10.3390\/ijms222111549","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T23:54:33Z","timestamp":1635292473000},"page":"11549","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cochlin Deficiency Protects Aged Mice from Noise-Induced Hearing Loss"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1661-9030","authenticated-orcid":false,"given":"Dorien","family":"Verdoodt","sequence":"first","affiliation":[{"name":"Department of Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk, Belgium"},{"name":"Laboratory of Experimental Hematology, Faculty of Medicine and Health Sciences, Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4349-2546","authenticated-orcid":false,"given":"Noa","family":"Peeleman","sequence":"additional","affiliation":[{"name":"Department of Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krystyna","family":"Szewczyk","sequence":"additional","affiliation":[{"name":"Department of Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Van Camp","sequence":"additional","affiliation":[{"name":"Centre of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp, 2650 Edegem, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1892-6499","authenticated-orcid":false,"given":"Peter","family":"Ponsaerts","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Hematology, Faculty of Medicine and Health Sciences, Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Van Rompaey","sequence":"additional","affiliation":[{"name":"Department of Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk, Belgium"},{"name":"Department of Otorhinolaryngology and Head & Neck Surgery, Antwerp University Hospital, 2650 Edegem, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.heares.2016.11.013","article-title":"Cellular mechanisms of noise-induced hearing loss","volume":"349","author":"Kurabi","year":"2017","journal-title":"Hear. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s10162-002-3036-4","article-title":"Lateral wall histopathology and endocochlear potential in the noise-damaged mouse cochlea","volume":"4","author":"Hirose","year":"2003","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1007\/s101620020028","article-title":"Dynamics of noise-induced cellular injury and repair in the mouse cochlea","volume":"3","author":"Wang","year":"2002","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1007\/s10162-014-0481-9","article-title":"Cochlin in normal middle ear and abnormal middle ear deposits in DFNA9 and Coch (G88E\/G88E) mice","volume":"15","author":"Robertson","year":"2014","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"108162","DOI":"10.1016\/j.heares.2020.108162","article-title":"On the pathophysiology of DFNA9: Effect of pathogenic variants in the COCH gene on inner ear functioning in human and transgenic mice","volume":"401","author":"Verdoodt","year":"2021","journal-title":"Hear. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.chom.2019.02.001","article-title":"Cleaved Cochlin Sequesters Pseudomonas aeruginosa and Activates Innate Immunity in the Inner Ear","volume":"25","author":"Jung","year":"2019","journal-title":"Cell Host Microbe."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1093\/hmg\/ddl022","article-title":"Cochlin immunostaining of inner ear pathologic deposits and proteomic analysis in DFNA9 deafness and vestibular dysfunction","volume":"15","author":"Robertson","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"14077","DOI":"10.1523\/JNEUROSCI.2845-09.2009","article-title":"Adding insult to injury: Cochlear nerve degeneration after \"temporary\" noise-induced hearing loss","volume":"29","author":"Kujawa","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00418-016-1436-5","article-title":"Characterisation of cochlear inflammation in mice following acute and chronic noise exposure","volume":"146","author":"Tan","year":"2016","journal-title":"Histochem. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.bbrc.2017.09.124","article-title":"Macrophage recruitment, but not interleukin 1 beta activation, enhances noise-induced hearing damage","volume":"493","author":"Mizushima","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s41431-017-0066-2","article-title":"Bi-allelic inactivating variants in the COCH gene cause autosomal recessive prelingual hearing impairment","volume":"26","author":"JanssensdeVarebeke","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_12","first-page":"189","article-title":"Novel Mutations in KCNQ4, LHFPL5 and COCH Genes in Iranian Families with Hearing Impairment","volume":"22","author":"Mehregan","year":"2019","journal-title":"Arch. Iran. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"JanssensdeVarebeke, S.M.J., Fransen, E., Bulen, B., Neesen, C., Devroye, K., van de Berg, R., Pennings, R.J.E., Topsakal, V., Vanderveken, O., and Van Camp, G. (2021). Genotype-Phenotype correlation study in a large series of patients carrying the p.Pro51Ser variant in the COCH gene (DFNA9). Part I: A cross-sectional study of hearing function in 111 carriers. Ear Hear., in Press.","DOI":"10.1097\/AUD.0000000000001099"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"JanssensdeVarebeke, S.M.J., Fransen, E., Bulen, B., Neesen, C., Devroye, K., van de Berg, R., Pennings, R.J.E., Topsakal, V., Vanderveken, O., and Van Camp, G. (2021). Genotype-Phenotype correlation study in a large series of patients carrying the p.Pro51Ser variant in the COCH gene (DFNA9). Part II: A prospective cross-sectional study of the vestibular phenotype in 111 carriers. Ear Hear., accepted minor revision.","DOI":"10.1097\/AUD.0000000000001070"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3426","DOI":"10.1093\/hmg\/ddn236","article-title":"A targeted Coch missense mutation: A knock-in mouse model for DFNA9 late-onset hearing loss and vestibular dysfunction","volume":"17","author":"Robertson","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.heares.2010.11.002","article-title":"Hearing and vestibular deficits in the Coch(-\/-) null mouse model: Comparison to the Coch(G88E\/G88E) mouse and to DFNA9 hearing and balance disorder","volume":"272","author":"Jones","year":"2011","journal-title":"Hear. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.immuni.2013.01.015","article-title":"Cochlin produced by follicular dendritic cells promotes antibacterial innate immunity","volume":"38","author":"Py","year":"2013","journal-title":"Immunity"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"670013","DOI":"10.3389\/fnmol.2021.670013","article-title":"Cochlin Deficiency Protects Against Noise-Induced Hearing Loss","volume":"14","author":"Seist","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e271","DOI":"10.1097\/MAO.0000000000001071","article-title":"Temporary and Permanent Noise-induced Threshold Shifts: A Review of Basic and Clinical Observations","volume":"37","author":"Ryan","year":"2016","journal-title":"Otol. Neurotol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1523\/JNEUROSCI.4985-05.2006","article-title":"Acceleration of age-related hearing loss by early noise exposure: Evidence of a misspent youth","volume":"26","author":"Kujawa","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3755","DOI":"10.1523\/JNEUROSCI.4460-15.2016","article-title":"Auditory Brainstem Response Latency in Noise as a Marker of Cochlear Synaptopathy","volume":"36","author":"Mehraei","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"134268","DOI":"10.1016\/j.neulet.2019.05.022","article-title":"Functional alteration of ribbon synapses in inner hair cells by noise exposure causing hidden hearing loss","volume":"707","author":"Liu","year":"2019","journal-title":"Neurosci Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6554","DOI":"10.1016\/S0021-9258(18)38153-5","article-title":"Limulus factor C. An endotoxin-sensitive serine protease zymogen with a mosaic structure of complement-like, epidermal growth factor-like, and lectin-like domains","volume":"266","author":"Muta","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4020","DOI":"10.1121\/1.5132545","article-title":"Inflammation associated with noise-induced hearing loss","volume":"146","author":"Frye","year":"2019","journal-title":"J. Acoust. Soc. Am."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.7150\/thno.49121","article-title":"Neutrophils infiltrate into the spiral ligament but not the stria vascularis in the cochlea during lipopolysaccharide-induced inflammation","volume":"11","author":"Bae","year":"2021","journal-title":"Theranostics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"580639","DOI":"10.3389\/fneur.2020.580639","article-title":"On the Role of Fibrocytes and the Extracellular Matrix in the Physiology and Pathophysiology of the Spiral Ligament","volume":"11","author":"Peeleman","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_27","unstructured":"Merchant, S.N. (2010). Schuknecht\u2019s Pathology of the Ear, People\u2019s Medical Publishing House."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1093\/hmg\/10.22.2493","article-title":"Inner ear localization of mRNA and protein products of COCH, mutated in the sensorineural deafness and vestibular disorder, DFNA9","volume":"10","author":"Robertson","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1007\/s00405-011-1484-3","article-title":"Acoustic overstimulation-induced apoptosis in fibrocytes of the cochlear spiral limbus of mice","volume":"268","author":"Cui","year":"2011","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-5955(98)00006-9","article-title":"Evidence for a medial K+ recycling pathway from inner hair cells","volume":"118","author":"Spicer","year":"1998","journal-title":"Hear. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s10162-009-0165-z","article-title":"Immunocytochemical traits of type IV fibrocytes and their possible relations to cochlear function and pathology","volume":"10","author":"Adams","year":"2009","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/S0378-5955(01)00250-7","article-title":"Genetic basis for susceptibility to noise-induced hearing loss in mice","volume":"155","author":"Davis","year":"2001","journal-title":"Hear. Res."},{"key":"ref_33","first-page":"19","article-title":"Genetic influences in individual susceptibility to noise: A review","volume":"5","author":"Davis","year":"2003","journal-title":"Noise Health"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Li, Y., Watanabe, K., Fujioka, M., and Ogawa, K. (2017). Characterization of slow-cycling cells in the mouse cochlear lateral wall. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179293"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1097\/WNR.0000000000000927","article-title":"Self-protection of type III fibrocytes against severe 3-nitropropionic-acid-induced cochlear damage in mice","volume":"29","author":"Li","year":"2018","journal-title":"Neuroreport"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1007\/s00109-012-0911-2","article-title":"A novel COCH mutation associated with autosomal dominant nonsyndromic hearing loss disrupts the structural stability of the vWFA2 domain","volume":"90","author":"Cho","year":"2012","journal-title":"J. Mol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Goel, M., Sienkiewicz, A.E., Picciani, R., Wang, J., Lee, R.K., and Bhattacharya, S.K. (2012). Cochlin, intraocular pressure regulation and mechanosensing. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034309"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1017\/S0952523805225099","article-title":"Cochlin and glaucoma: A mini-review","volume":"22","author":"Bhattacharya","year":"2005","journal-title":"Vis. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.preteyeres.2007.06.002","article-title":"Cochlin in the eye: Functional implications","volume":"26","author":"Picciani","year":"2007","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e1768","DOI":"10.21769\/BioProtoc.1768","article-title":"Mouse Auditory Brainstem Response Testing","volume":"6","author":"Akil","year":"2016","journal-title":"Bio-Protocol"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11549\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:24:02Z","timestamp":1760167442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,26]]},"references-count":40,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222111549"],"URL":"https:\/\/doi.org\/10.3390\/ijms222111549","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,26]]}}}