Connexin 30 deletion exacerbates cochlear senescence and age-related hearing loss

Fabiola Paciello; Veronica Zorzi; Marcello Raspa; Ferdinando Scavizzi; Claudio Grassi; Fabio Mammano; Anna Rita Fetoni

doi:10.3389/fcell.2022.950837

Connexin 30 deletion exacerbates cochlear senescence and age-related hearing loss

Front Cell Dev Biol. 2022 Aug 9:10:950837. doi: 10.3389/fcell.2022.950837. eCollection 2022.

Authors

Fabiola Paciello^{1

2}, Veronica Zorzi³, Marcello Raspa³, Ferdinando Scavizzi³, Claudio Grassi^{1

2}, Fabio Mammano^{3

4}, Anna Rita Fetoni^{5

6}

Affiliations

¹ Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.
² Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
³ CNR Institute of Biochemistry and Cell Biology, Monterotondo (RM), Italy.
⁴ Department of Physics and Astronomy, University of Padova, Padova, Italy.
⁵ Department of Otolaryngology Head and Neck Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.
⁶ Unit of Audiology, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples Federico II, Naples, Italy.

Abstract

Pathogenic mutations in the Gjb2 and Gjb6 genes, encoding connexin 26 (Cx26) and connexin 30 (Cx30), respectively, have been linked to the most frequent monogenic hearing impairment, nonsyndromic hearing loss, and deafness DFNB1. It is known that Cx26 plays an important role in auditory development, while the role of Cx30 in hearing remains controversial. Previous studies found that partial deletion of Cx26 can accelerate age-related hearing loss (ARHL), a multifactorial complex disorder, with both environmental and genetic factors contributing to the etiology of the disease. Here, we investigated the role of Cx30 in cochlear-aging processes using a transgenic mouse model with total deletion of Cx30 (Cx30 ΔΔ mice), in which Cx30 was removed without perturbing the surrounding sequences. We show that these mice are affected by exacerbated ARHL, with increased morphological cochlear damage, oxidative stress, inflammation, and vascular dysfunctions. Overall, our data demonstrate that Cx30 deletion can be considered a genetic risk factor for ARHL, making cochlear structures more susceptible to aging processes.

Keywords: connexins; genetic risk factors; inflammation; inner ear; oxidative stress; presbycusis; vascular dysfunction.