Doxepin Mitigates Noise ‐induced Neuronal Damage in Primary Auditory Cortex of Mice via Suppression of Acid Sphingomyelinase/Ceramide Pathway

ABSTRACT Neuronal damage in primary auditory cortex (A1) underlies complex manifestations of noise exposure, prevention of which is critical for health maintenance. Acid sphingomyelinase (ASM) catalyzes generation of ceramide (Cer) which if over‐activated mediates neuronal disorders in various diseases. Tricyclic antidepressants (TCAs), by restraining ASM/Cer, benefits multiple neuronal anomalies, so we aimed to elucidate the effect of TCA on noise induced hearing loss and auditory cortex derangement, unraveling mechanism involved. The mice were exposed to noise with frequencies of 20–20 KHz and intensity of 95 dB. Doxepin hydrochloride (DOX), a kind of TCAs, was given intragastrically by 5 mg kg−1 days−1. Morphology of neurons was examined using hematoxylin‐eosin (HE) and Nissl staining. Apoptosis was assayed through transferase‐mediated dUTP nick end labeling (TUNEL). The content of ASM, Cer or acid ceramidase (AC) was detected by western blot and immunohistochemistry analysis. We demonstrated intense, broad band noise caused upward shift of auditory brainstem response (ABR) threshold to sound over frequencies 4–32 KHz, with prominent morphologic changes and enhanced apoptosis in neurons of primary auditory cortex (A1) (P < 0.05). DOX partly restored noise‐caused hearing loss alleviating morphologic changes or apoptosis remarkably (P < 0.05). Both ASM and Cer abundance were elevated significantly by noise which was reversed upon DOX treatment...
Source: The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology - Category: Molecular Biology Authors: Tags: Full Length Article Source Type: research