Wenji Zhai , Xiaojing Kuang , Jie Wu , Liheng Li , Bo Li , Ruishuang Geng , Tihua Zheng , Qingyin Zheng
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引用次数: 0
Abstract
Noise-induced hearing loss (NIHL) is a common auditory disorder driven by calcium overload, oxidative stress, and apoptosis in cochlear sensory hair cells. The transient receptor potential canonical 6 (TRPC6), a nonselective cation channel that can be activated by norepinephrine, is implicated in calcium influx and associated cellular damage. This study explores the protective effects of clonidine, an FDA-approved α2-adrenergic receptor agonist that reduces sympathetic nervous system activity and norepinephrine release, on NIHL in mice. Clonidine treatment significantly preserved hearing thresholds, reduced damage to outer hair cells and ribbon synapses, and suppressed TRPC6 channel activation induced by noise exposure. Mechanistically, clonidine alleviated calcium influx, inhibited the calcium-dependent MLCK-MRLC signaling pathway, and attenuated oxidative stress and apoptosis in cochlear hair cells. Molecular docking analyses demonstrated strong binding between norepinephrine and TRPC6, elucidating the regulatory role of clonidine in calcium signaling. These findings highlight clonidine's potential to prevent NIHL by maintaining intracellular calcium homeostasis and reducing cochlear damage via the modulation of norepinephrine and TRPC6 activity. TRPC6 emerges as a promising therapeutic target for preventing and managing noise-induced auditory dysfunction.
期刊介绍:
The aim of the journal is to provide a forum for papers concerned with basic peripheral and central auditory mechanisms. Emphasis is on experimental and clinical studies, but theoretical and methodological papers will also be considered. The journal publishes original research papers, review and mini- review articles, rapid communications, method/protocol and perspective articles.
Papers submitted should deal with auditory anatomy, physiology, psychophysics, imaging, modeling and behavioural studies in animals and humans, as well as hearing aids and cochlear implants. Papers dealing with the vestibular system are also considered for publication. Papers on comparative aspects of hearing and on effects of drugs and environmental contaminants on hearing function will also be considered. Clinical papers will be accepted when they contribute to the understanding of normal and pathological hearing functions.