| First Author | Seist R | Year | 2021 |
| Journal | Front Mol Neurosci | Volume | 14 |
| Pages | 670013 | PubMed ID | 34108864 |
| Mgi Jnum | J:314129 | Mgi Id | MGI:6813738 |
| Doi | 10.3389/fnmol.2021.670013 | Citation | Seist R, et al. (2021) Cochlin Deficiency Protects Against Noise-Induced Hearing Loss. Front Mol Neurosci 14:670013 |
| abstractText | 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. |
