Eaton-Peabody Laboratories, Massachusetts Eye and Ear, 243 Charles St., Boston, MA, 02114-3096, USA.
Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, 02115, USA.
Sci Rep. 2020 Nov 17;10(1):19945. doi: 10.1038/s41598-020-76553-w.
Overexposure to intense noise can destroy the synapses between auditory nerve fibers and their hair cell targets without destroying the hair cells themselves. In adult mice, this synaptopathy is immediate and largely irreversible, whereas, in guinea pigs, counts of immunostained synaptic puncta can recover with increasing post-exposure survival. Here, we asked whether this recovery simply reflects changes in synaptic immunostaining, or whether there is actual retraction and extension of neurites and/or synaptogenesis. Analysis of the numbers, sizes and spatial distribution of pre- and post-synaptic markers on cochlear inner hair cells, in guinea pigs surviving from 1 day to 6 months after a synaptopathic exposure, shows dramatic synaptic re-organization during the recovery period in which synapse counts recover from 16 to 91% of normal in the most affected regions. Synaptic puncta move all over the hair cell membrane during recovery, translocating far from their normal positions at the basolateral pole, and auditory-nerve terminals extend towards the hair cell's apical end to re-establish contact with them. These observations provide stronger evidence for spontaneous neural regeneration in a mature mammalian cochlea than can be inferred from synaptic counts alone.
过度暴露于强烈噪声会破坏听神经纤维与其毛细胞靶之间的突触，而不会破坏毛细胞本身。在成年小鼠中，这种突触病是即刻的，且在很大程度上是不可逆转的，而在豚鼠中，免疫染色突触小体的计数可以随着暴露后存活时间的增加而恢复。在这里，我们想知道这种恢复是否仅仅反映了突触免疫染色的变化，还是神经突的回缩和延伸以及/或者突触发生实际上发生了变化。对在突触病暴露后 1 天至 6 个月存活下来的豚鼠耳蜗内毛细胞的前突触和后突触标记物的数量、大小和空间分布进行分析，显示在恢复期间发生了显著的突触重组，其中在受影响最严重的区域，突触计数从正常的 16%恢复到 91%。在恢复过程中，突触小体在整个毛细胞膜上移动，从基底外侧极的正常位置迁移很远，听觉神经末梢向毛细胞的顶端延伸，以重新与它们建立联系。这些观察结果为成熟哺乳动物耳蜗中的自发神经再生提供了比仅从突触计数推断更强的证据。
