AUTHOR=Seist Richard , Landegger Lukas D. , Robertson Nahid G. , Vasilijic Sasa , Morton Cynthia C. , Stankovic Konstantina M. TITLE=Cochlin Deficiency Protects Against Noise-Induced Hearing Loss JOURNAL=Frontiers in Molecular Neuroscience VOLUME=14 YEAR=2021 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2021.670013 DOI=10.3389/fnmol.2021.670013 ISSN=1662-5099 ABSTRACT=

Cochlin is the most abundant protein in the inner ear. To study its function in response to noise trauma, we exposed adolescent wild-type (Coch^+/+) and cochlin knock-out (Coch^–/–) mice to noise (8–16 kHz, 103 dB SPL, 2 h) that causes a permanent threshold shift and hair cell loss. Two weeks after noise exposure, Coch^–/– mice had substantially less elevation in noise-induced auditory thresholds and hair cell loss than Coch⁺^/⁺ mice, consistent with cochlin deficiency providing protection from noise trauma. Comparison of pre-noise exposure thresholds of auditory brain stem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) in Coch^–/– mice and Coch⁺^/⁺ littermates revealed a small and significant elevation in thresholds of Coch^–/– mice, overall consistent with a small conductive hearing loss in Coch^–/– mice. We show quantitatively that the pro-inflammatory component of cochlin, LCCL, is upregulated after noise exposure in perilymph of wild-type mice compared to unexposed mice, as is the enzyme catalyzing LCCL release, aggrecanase1, encoded by Adamts4. We further show that upregulation of pro-inflammatory cytokines in perilymph and cochlear soft-tissue after noise exposure is lower in cochlin knock-out than wild-type mice. Taken together, our data demonstrate for the first time that cochlin deficiency results in conductive hearing loss that protects against physiologic and molecular effects of noise trauma.