Kobel Megan, Le Prell Colleen G, Liu Jennifer, Hawks John W, Bao Jianxin
Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH 442722, USA.
Callier Center for Communication Disorders, University of Texas at Dallas, Dallas, TX 75235, USA.
Hear Res. 2017 Jun;349:148-154. doi: 10.1016/j.heares.2016.12.008. Epub 2016 Dec 19.
For decades, we have presumed the death of hair cells and spiral ganglion neurons are the main cause of hearing loss and difficulties understanding speech in noise, but new findings suggest synapse loss may be the key contributor. Specifically, recent preclinical studies suggest that the synapses between inner hair cells and spiral ganglion neurons with low spontaneous rates and high thresholds are the most vulnerable subcellular structures, with respect to insults during aging and noise exposure. This cochlear synaptopathy can be "hidden" because this synaptic loss can occur without permanent hearing threshold shifts. This new discovery of synaptic loss opens doors to new research directions. Here, we review a number of recent studies and make suggestions in two critical future research directions. First, based on solid evidence of cochlear synaptopathy in animal models, it is time to apply molecular approaches to identify the underlying molecular mechanisms; improved understanding is necessary for developing rational, effective therapies against this cochlear synaptopathy. Second, in human studies, the data supporting cochlear synaptopathy are indirect although rapid progress has been made. To fully identify changes in function that are directly related this hidden synaptic damage, we argue that a battery of tests including both electrophysiological and behavior tests should be combined for diagnosis of "hidden hearing loss" in clinical studies. This new approach may provide a direct link between cochlear synaptopathy and perceptual difficulties.
几十年来，我们一直认为毛细胞和螺旋神经节神经元的死亡是听力损失以及在噪声环境中理解言语困难的主要原因，但新的研究结果表明，突触损失可能是关键因素。具体而言，最近的临床前研究表明，自发率低且阈值高的内毛细胞与螺旋神经节神经元之间的突触是最易受损的亚细胞结构，在衰老和噪声暴露过程中易受损伤。这种耳蜗突触病变可能是“隐匿性的”，因为这种突触损失可能在听力阈值无永久性变化的情况下发生。突触损失这一新发现为新的研究方向打开了大门。在此，我们回顾一些近期研究，并就未来两个关键研究方向提出建议。首先，基于动物模型中耳蜗突触病变的确凿证据，现在是时候应用分子方法来确定潜在的分子机制了；深入了解这些机制对于开发针对这种耳蜗突触病变的合理、有效疗法至关重要。其次，在人体研究中，尽管已取得快速进展，但支持耳蜗突触病变的数据是间接的。为了全面识别与这种隐匿性突触损伤直接相关的功能变化，我们认为在临床研究中应结合一系列包括电生理和行为测试在内的检测方法来诊断“隐匿性听力损失”。这种新方法可能为耳蜗突触病变与感知困难之间提供直接联系。
