Scar Formation and Debris Elimination during Hair Cell Degeneration in the Adult DTR Mouse.
Scar Formation and Debris Elimination during Hair Cell Degeneration in the Adult DTR Mouse.
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DOI：
10.1016/j.neuroscience.2020.11.041
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发表时间：
2021-01-15
期刊：
影响因子：
3.3
通讯作者：
Raphael Y
中科院分区：
文献类型：
--
作者：
Lee S;Kurioka T;Lee MY;Beyer LA;Swiderski DL;Ritter KE;Raphael Y
哺乳动物内耳的听觉感觉上皮是高度组织化的结构，其包含感觉毛细胞（HC）和非感觉支持细胞（SC）。在耳蜗损伤如过度刺激或耳毒性药物后，HC部分丧失后，SC密封腔上皮表面（网状层）并重组其细胞模式。在这里，我们调查了感觉上皮的变化后，快速和严重的耳蜗损伤的白喉毒素受体（DTR）小鼠，白喉毒素（DT）注射导致HC特异性病变，导致完全HC损失。我们发现DT诱导的选择性HC消融可能导致瘢痕形成和顶端细胞-细胞粘附以及紧密连接重组的模式，类似于其他类型的耳蜗损伤后发生的情况。普雷斯廷，一种外部HC特异性蛋白，在DT诱导损伤后2个月内，在SC膨胀以填充死亡HC空出的空间的部位以无定形团块存在。许多普雷斯廷团块似乎占据了SC内的空间，表明SC参与了DTR耳聋模型中HC尸体的去除过程。普雷斯廷团块分布于SC的不同区域，沿沿着，既存在于SC内部，也存在于SC之间的细胞间隙。研究结果表明，DTR耳聋模型中的HC消除遵循与过度刺激或耳毒性模型相似的机制，使得DTR小鼠有助于理解HC消除的过程以及SC在此过程中的作用。
The auditory sensory epithelium of the mammalian inner ear is a highly organized structure that contains sensory hair cells (HCs) and non-sensory supporting cells (SCs). Following the partial loss of HCs after cochlear insults such as overstimulation or ototoxic drugs, SCs seal the luminal epithelial surface (reticular lamina) and reorganize its cellular pattern. Here we investigated the changes in the sensory epithelium following a rapid and severe cochlear insult in the diphtheria toxin receptor (DTR) mouse, where diphtheria toxin (DT) injection leads to a HC-specific lesion resulting in a complete HC loss. We found that DT-induced selective HC ablation could lead to a pattern of scar formation and apical cell-cell adherens and tight junction reorganization similar to that occurring after other types of cochlear insult. Prestin, an outer HC-specific protein, was present in amorphous clumps at the sites where SCs had expanded to fill the spaces vacated by the dead HCs for up to 2 months after the DT induced lesion. Many of the prestin clumps appeared to occupy spaces within SCs, suggesting that SCs participate in the removal process of HC corpses in the DTR deafness model. Prestin clumps could be seen in different areas all along the length of the SCs, and appeared to be inside the SCs as well as in the inter-cellular spaces between SCs. The findings suggest that HC elimination in the DTR deafness model follows a mechanism similar to that in overstimulation or ototoxicity models, making the DTR mouse useful for understanding the process underlying HC elimination and the role of SCs in this process.
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影响因子：
2.8
作者：
CARLISLE, L;ZAJIC, G;THORNE, PR
通讯作者：
THORNE, PR
DOI：
10.1002/neu.10002
发表时间：
2002-02-05
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Gale, JE;Meyers, JR;Corwin, JT
通讯作者：
Corwin, JT
影响因子：
--
作者：
RAPHAEL, Y;ALTSCHULER, RA
通讯作者：
ALTSCHULER, RA
影响因子：
2.8
作者：
RAPHAEL, Y;ALTSCHULER, RA
通讯作者：
ALTSCHULER, RA
DOI：
10.1007/s10162-014-0480-x
发表时间：
2014-12-01
影响因子：
2.4
作者：
Anttonen, Tommi;Belevich, Ilya;Pirvola, Ulla
通讯作者：
Pirvola, Ulla