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Cochlin Deficiency Protects Against Noise-Induced Hearing Loss.

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.

SUBMITTER: Seist R

PROVIDER: S-EPMC8180578 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Cochlin Deficiency Protects Aged Mice from Noise-Induced Hearing Loss.

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2024-06-24 | GSE252285 | GEO

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