Selective hair cell ablation and noise exposure lead to different patterns of changes in the cochlea and the cochlear nucleus.
Selective hair cell ablation and noise exposure lead to different patterns of changes in the cochlea and the cochlear nucleus.
复制标题
DOI：
10.1016/j.neuroscience.2016.07.001
复制
发表时间：
2016-09-22
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：
Kurioka T;Lee MY;Heeringa AN;Beyer LA;Swiderski DL;Kanicki AC;Kabara LL;Dolan DF;Shore SE;Raphael Y
在听觉毛细胞（HC）损失的实验动物模型中，诸如噪声或耳毒性药物的损伤通常导致非感觉细胞和神经成分的继发性改变或变性，包括螺旋神经节神经元密度降低、听觉神经纤维脱髓鞘以及耳蜗核中细胞数量和神经支配模式的改变。然而，目前尚不清楚是否HC的损失单独导致这些听觉通路的神经成分的继发性变性。为了阐明这一问题，我们研究了耳蜗损伤后的中央组件的变化，使用白喉毒素受体（DTR）小鼠，仅在HC中表达DTR，并在注射白喉毒素（DT）时表现出完全的HC损失。我们发现，DT诱导的HC消融对听觉神经元、中枢突触末梢和髓鞘的存活没有显著影响，尽管HC完全丧失和深度耳聋。与此相反，噪声暴露引起的突触，髓鞘和CN组织的显着变化，即使没有损失的内部HC。我们观察到听觉通路中的神经元大小减少，包括外周轴突、螺旋神经节神经元和耳蜗核神经元，这可能是由于来自耳蜗的输入丢失。两者合计，选择性HC消融和噪声暴露在听觉通路中表现出不同的病理模式，并且HC的存在对于维持中枢突触连接和髓鞘形成并不重要。
In experimental animal models of auditory hair cell (HC) loss, insults such as noise or ototoxic drugs often lead to secondary changes or degeneration in non-sensory cells and neural components, including reduced density of spiral ganglion neurons, demyelination of auditory nerve fibers and altered cell numbers and innervation patterns in the cochlear nucleus. However, it is not clear whether loss of HCs alone leads to secondary degeneration in these neural components of the auditory pathway. To elucidate this issue, we investigated changes of central components after cochlear insults specific to HCs using diphtheria toxin receptor (DTR) mice expressing DTR only in HCs and exhibiting complete HC loss when injected with diphtheria toxin (DT). We showed that DT-induced HC ablation has no significant impacts on the survival of auditory neurons, central synaptic terminals, and myelin, despite complete HC loss and profound deafness. In contrast, noise exposure induced significant changes in synapses, myelin and CN organization even without loss of inner HCs. We observed a decrease of neuronal size in the auditory pathway, including peripheral axons, spiral ganglion neurons, and cochlear nucleus neurons, likely due to loss of input from the cochlea. Taken together, selective HC ablation and noise exposure showed different patterns of pathology in the auditory pathway and the presence of HCs is not essential for the maintenance of central synaptic connectivity and myelination.