Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish.
Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish.
复制标题
机械过度刺激会导致急性损伤和突触损失，然后在幼虫斑马鱼的横向神经瘤中快速恢复。
DOI：
10.7554/elife.69264
复制
发表时间：
2021-10-19
期刊：
影响因子：
7.7
通讯作者：
Sheets L
中科院分区：
文献类型：
--
作者：
Holmgren M;Ravicz ME;Hancock KE;Strelkova O;Kallogjeri D;Indzhykulian AA;Warchol ME;Sheets L
过量的噪音会损害感觉毛细胞，导致与听觉神经的突触连接丧失，在某些情况下，毛细胞死亡。机械诱导的毛细胞损伤和随后的修复的细胞机制尚未完全理解。斑马鱼幼鱼神经乳突中的毛细胞在结构和功能上与哺乳动物的毛细胞相当，但在耳毒性损伤后会进行稳健的再生。因此，我们开发了一个模型，机械诱导的毛细胞损伤，在这个高度听话的系统。自由游泳的幼虫暴露于强水波刺激2小时显示机械损伤神经瘤，包括传入神经突起回缩，受损的毛束，和减少机械转导。在明显完整的暴露神经丘中观察到突触丢失，并且这种丢失通过抑制谷氨酸摄取而加剧。机械损伤也引起炎症反应和巨噬细胞募集。值得注意的是，神经肥大毛细胞形态和机械转导在暴露后数小时内恢复，表明严重受损的神经肥大进行修复。我们的研究结果表明，机械损伤的侧线神经瘤的功能变化和突触丢失，在噪声暴露的哺乳动物耳朵中观察到的损害的关键特征。然而，与哺乳动物的耳朵不同，神经乳突的机械损伤是迅速可逆的。
Excess noise damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and, in some cases, hair-cell death. The cellular mechanisms underlying mechanically induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following ototoxic damage. We therefore developed a model for mechanically induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water wave stimulus for 2 hr displayed mechanical injury to neuromasts, including afferent neurite retraction, damaged hair bundles, and reduced mechanotransduction. Synapse loss was observed in apparently intact exposed neuromasts, and this loss was exacerbated by inhibiting glutamate uptake. Mechanical damage also elicited an inflammatory response and macrophage recruitment. Remarkably, neuromast hair-cell morphology and mechanotransduction recovered within hours following exposure, suggesting severely damaged neuromasts undergo repair. Our results indicate functional changes and synapse loss in mechanically damaged lateral-line neuromasts that share key features of damage observed in noise-exposed mammalian ear. Yet, unlike the mammalian ear, mechanical damage to neuromasts is rapidly reversible.