Cochlin Deficiency Protects Aged Mice from Noise-Induced Hearing Loss

Abstract

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−/−) 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−/− 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.

Understanding the role of inflammation in sensorineural hearing loss: Current goals and future prospects

“…This inflammatory response involves the rapid recruitment and infiltration of inflammatory cells from the systemic circulation. Various inflammatory genes are associated with cochlear inflammation, but their exact molecular pathways and mechanisms remain unclear [101] . C‐X‐C motif chemokine ligand 1 (CXCL1) is expressed in neutrophils, macrophages, and epithelial cells.…”

“…Various inflammatory genes are associated with cochlear inflammation, but their exact molecular pathways and mechanisms remain unclear. [101] C-X-C motif chemokine ligand 1 (CXCL1) is expressed in neutrophils, macrophages, and epithelial cells. Recent studies have found that Cxcl1 is expressed in columnar, Deiters, interdental, and vestibular Sertoli cells in CBA/CaJ mice.…”

Advances in otolith-related protein research

“…Overexpression of cochlin in the early stage of Meniere's disease may be one of the causes of intractable Meniere's disease (Calzada et al, 2012). Verdoodt et al (2021) found that the loss of Cochlin had a protective effect on hearing threshold after noise exposure in a Cochlin knockout mouse model, but the mutation of cochlin gene encoding cochlin protein can lead to DFNA9, an autosomal dominant non-syndromic sensorineural deafness with vestibular involvement. Cochlin, which is defective in 10.3389/fnins.2022.956200…”

“…Expressed in the cochlea and vestibular organs (mainly the utricle and saccule) (Weigele et al, 2015) Maintains normal otolith growth and is directly related to otolith shape (Murayama et al, 2005) Associated with movement disorders (Weigele et al, 2015) Cochlin Expressed in the cochlea and vestibule (mainly in spiral ligament, spiral bone and spiral rim of the inner ear) (Rhyu et al, 2020) Main otolith constituent, determinant of calcium carbonate crystalline formation (Leventea et al, 2021) Its overexpression is associated with Ménière's disease (Calzada et al, 2012); associated with conductive hearing loss and vestibular dysfunction (Leventea et al, 2021;Verdoodt et al, 2021); diagnosis of exolymphatic fistula (Xiong et al, 2020); diagnosis of exolymphatic fistula Otogelin Expression in the cochlea and vestibule (Avan et al, 2019) Anchoring of the otolith (Schraders et al, 2012;Whitfield, 2020); stabilization of the cochlear covering membrane (Avan et al, 2019) Deficiency leading to otolith detachment and instability of the cochlear covering membrane; OTOG mutation leading to DFNB18B hereditary deafness (Avan et al, 2019) α-tectorin and β-tectorin Non-collagenous glycoprotein component of the Cochlear Covering Membrane (TM) (Andrade et al, 2016) Adherence of TM to the spiral rim and to the stereocilia of the outer hair cells of the cochlea (Andrade et al, 2016) Determinants of otolith formation (Asgharzade et al, 2011) Deficiency can lead to varying degrees of hearing loss (Asgharzade et al, 2017) β-tectorin deficiency can lead to imbalance (Zou et al, 2006) Otopetrin1 and Otopetrin-2 Expression in the cochlea and vestibule (Kim et al, 2010;Tu et al, 2018;Khan et al, 2019;Lopez et al, 2019) Maintains nucleus formation, and growth of otoliths (Kim et al, 2010); a proton-selective channel involved in gravity sensing in the vestibular system Lack of otopetrin-1 knockout in mice leads to vestibular dysfunction (Khan et al, 2019).…”