Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, PI, Italy.
IRCCS, Istituto di Ricovero e Cura a Carattere Scientifico, Neuromed, 86077 Pozzilli, IS, Italy.
Int J Mol Sci. 2023 Nov 23;24(23):16664. doi: 10.3390/ijms242316664.
Tinnitus is the perception of noise in the absence of acoustic stimulation (phantom noise). In most patients suffering from chronic peripheral tinnitus, an alteration of outer hair cells (OHC) starting from the stereocilia (SC) occurs. This is common following ototoxic drugs, sound-induced ototoxicity, and acoustic degeneration. In all these conditions, altered coupling between the tectorial membrane (TM) and OHC SC is described. The present review analyzes the complex interactions involving OHC and TM. These need to be clarified to understand which mechanisms may underlie the onset of tinnitus and why the neuropathology of chronic degenerative tinnitus is similar, independent of early triggers. In fact, the fine neuropathology of tinnitus features altered mechanisms of mechanic-electrical transduction (MET) at the level of OHC SC. The appropriate coupling between OHC SC and TM strongly depends on autophagy. The involvement of autophagy may encompass degenerative and genetic tinnitus, as well as ototoxic drugs and acoustic trauma. Defective autophagy explains mitochondrial alterations and altered protein handling within OHC and TM. This is relevant for developing novel treatments that stimulate autophagy without carrying the burden of severe side effects. Specific phytochemicals, such as curcumin and berberin, acting as autophagy activators, may mitigate the neuropathology of tinnitus.
耳鸣是指在没有声音刺激（幻听）的情况下感知到噪音。大多数患有慢性外周性耳鸣的患者，其外毛细胞 (OHC) 从静纤毛 (SC) 开始发生改变。这在耳毒性药物、声音诱导的耳毒性和声音退化后很常见。在所有这些情况下，都描述了镫骨膜 (TM) 和 OHC SC 之间的耦合改变。本综述分析了涉及 OHC 和 TM 的复杂相互作用。这些需要被阐明，以便理解哪些机制可能是耳鸣发生的基础，以及为什么慢性退行性耳鸣的神经病理学是相似的，而与早期触发因素无关。事实上，耳鸣的精细神经病理学特征是 OHC SC 水平上机械-电转换 (MET) 的机制改变。OHC SC 和 TM 之间的适当耦合强烈依赖于自噬。自噬的参与可能包括退行性和遗传性耳鸣，以及耳毒性药物和声音创伤。自噬缺陷解释了线粒体改变以及 OHC 和 TM 内蛋白质处理的改变。这对于开发新的治疗方法很重要，这些方法可以在没有严重副作用负担的情况下刺激自噬。特定的植物化学物质，如姜黄素和小檗碱，作为自噬激活剂，可能减轻耳鸣的神经病理学。
