Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
Glia. 2022 Apr;70(4):768-791. doi: 10.1002/glia.24138. Epub 2021 Dec 29.
The auditory nerve (AN) of the inner ear is the primary conveyor of acoustic information from sensory hair cells to the brainstem. Approximately 95% of peripheral AN fibers are myelinated by glial cells. The integrity of myelin and the glial-associated paranodal structures at the node of Ranvier is critical for normal AN activity and axonal survival and function in the central auditory nervous system. However, little is known about the node of Ranvier's spatiotemporal development in the AN, how the aging process (or injury) affects the activity of myelinating glial cells, and how downstream alterations in myelin and paranodal structure contribute to AN degeneration and sensorineural hearing loss. Here, we characterized two types of Ranvier nodes-the axonal node and the ganglion node-in the mouse peripheral AN, and found that they are distinct in several features of postnatal myelination and age-related degeneration. Cellular, molecular, and structure-function correlations revealed that the two node types are each critical for different aspects of peripheral AN function. Neural processing speed and synchrony is associated with the length of the axonal node, while stimulus level-dependent amplitude growth and action potentials are associated with the ganglion node. Moreover, our data indicate that dysregulation of glial cells (e.g., satellite cells) and degeneration of the ganglion node structure are an important new mechanism of age-related hearing loss.
内耳的听神经 (AN) 是将声信息从感觉毛细胞传递到脑干的主要导体。大约 95%的外周 AN 纤维被神经胶质细胞髓鞘化。施旺细胞相关的髓鞘和结旁结构的完整性对于 AN 活动以及中枢听觉神经系统中的轴突存活和功能至关重要。然而，对于 AN 中结的时空发育、衰老过程（或损伤）如何影响髓鞘形成胶质细胞的活性，以及髓鞘和结旁结构的下游改变如何导致 AN 变性和感觉神经性听力损失，我们知之甚少。在这里，我们描述了小鼠外周 AN 中的两种Ranvier 结——轴突结和神经节结，并发现它们在出生后髓鞘化和与年龄相关的变性的几个特征上存在差异。细胞、分子和结构功能相关性表明，这两种结类型对于外周 AN 功能的不同方面都是至关重要的。神经处理速度和同步性与轴突结的长度有关，而刺激水平依赖性的幅度增长和动作电位与神经节结有关。此外，我们的数据表明，神经胶质细胞（如卫星细胞）的失调和神经节结结构的变性是与年龄相关的听力损失的一个重要新机制。
