Wise Andrew K, Pujol Remy, Landry Thomas G, Fallon James B, Shepherd Robert K
The Bionics Institute, 384-388 Albert Street, East Melbourne, Victoria, 3002, Australia.
Department of Medical Bionics, University of Melbourne, Melbourne, Australia.
J Assoc Res Otolaryngol. 2017 Dec;18(6):751-769. doi: 10.1007/s10162-017-0631-y. Epub 2017 Jul 17.
Sensorineural hearing loss is commonly caused by damage to cochlear sensory hair cells. Coinciding with hair cell degeneration, the peripheral fibres of type I spiral ganglion neurons (SGNs) that normally form synaptic connections with the inner hair cell gradually degenerate. We examined the time course of these degenerative changes in type I SGNs and their satellite Schwann cells at the ultrastructural level in guinea pigs at 2, 6, and 12 weeks following aminoglycoside-induced hearing loss. Degeneration of the peripheral fibres occurred prior to the degeneration of the type I SGN soma and was characterised by shrinkage of the fibre followed by retraction of the axoplasm, often leaving a normal myelin lumen devoid of axoplasmic content. A statistically significant reduction in the cross-sectional area of peripheral fibres was evident as early as 2 weeks following deafening (p < 0.001, ANOVA). This was followed by a decrease in type I SGN density within Rosenthal's canal that was statistically significant 6 weeks following deafening (p < 0.001, ANOVA). At any time point examined, few type I SGN soma were observed undergoing degeneration, implying that once initiated, soma degeneration was rapid. While there was a significant reduction in soma area as well as changes to the morphology of the soma, the ultrastructure of surviving type I SGN soma appeared relatively normal over the 12-week period following deafening. Satellite Schwann cells exhibited greater survival traits than their type I SGN; however, on loss of neural contact, they reverted to a non-myelinating phenotype, exhibiting an astrocyte-like morphology with the formation of processes that appeared to be searching for new neural targets. In 6- and 12-week deafened cochlea, we observed cellular interaction between Schwann cell processes and residual SGNs that distorted the morphology of the SGN soma. Understanding the response of SGNs, Schwann cells, and the complex relationship between them following aminoglycoside deafening is important if we are to develop effective therapeutic techniques designed to rescue SGNs.
感音神经性听力损失通常由耳蜗感觉毛细胞受损引起。与毛细胞退化同时发生的是，通常与内毛细胞形成突触连接的I型螺旋神经节神经元（SGNs）的外周纤维逐渐退化。我们在豚鼠氨基糖苷类药物致聋后2周、6周和12周，在超微结构水平上研究了I型SGNs及其卫星施万细胞这些退化性变化的时间进程。外周纤维的退化发生在I型SGN胞体退化之前，其特征是纤维收缩，随后轴浆回缩，常常留下一个没有轴浆内容物的正常髓鞘腔。早在致聋后2周，外周纤维横截面积就出现了统计学上的显著减少（p < 0.001，方差分析）。随后，罗森塔尔管内I型SGN密度下降，在致聋后6周具有统计学意义（p < 0.001，方差分析）。在任何检查的时间点，很少观察到I型SGN胞体发生退化，这意味着一旦开始，胞体退化很快。虽然胞体面积有显著减少以及胞体形态发生变化，但在致聋后的12周内，存活的I型SGN胞体的超微结构看起来相对正常。卫星施万细胞比其I型SGN表现出更强的存活特性；然而，在失去神经接触后，它们会转变为非髓鞘形成表型，表现出星形胶质细胞样形态，形成似乎在寻找新神经靶点的突起。在致聋6周和12周的耳蜗中，我们观察到施万细胞突起与残留SGNs之间的细胞相互作用，这扭曲了SGN胞体的形态。如果我们要开发旨在挽救SGNs的有效治疗技术，了解氨基糖苷类药物致聋后SGNs、施万细胞的反应以及它们之间的复杂关系是很重要的。
