Regenerative Effect of a ROCK Inhibitor, Y-27632, on Excitotoxic Trauma in an Organotypic Culture of the Cochlea.
Regenerative Effect of a ROCK Inhibitor, Y-27632, on Excitotoxic Trauma in an Organotypic Culture of the Cochlea.
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DOI：
10.3389/fncel.2020.572434
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发表时间：
2020
影响因子：
5.3
通讯作者：
Kakehata S
中科院分区：
文献类型：
--
作者：
Koizumi Y;Ito T;Mizutari K;Kakehata S
在过去，大多数内耳疾病被认为是在随后进展为继发性神经变性之前始于耳蜗感觉上皮的损伤。然而，最近的研究表明，初级突触的损失伴随着外周轴突的兴奋性毒性变性可能是感音神经性听力损失的潜在病理。据报道，Rho相关的卷曲螺旋蛋白激酶（ROCK）抑制对突触通路具有神经保护和再生作用。因此，我们分析了使用Y-27632在螺旋神经节神经元中的外周轴突损伤模型中ROCK抑制的作用，所述螺旋神经节神经元使用谷氨酸激动剂N-甲基-D-天冬氨酸（NMDA）和红藻氨酸来诱导受损耳蜗中的兴奋性毒性创伤。在用Y-27632处理的耳蜗中投射到毛细胞的轴突的数量显著大于仅用NMDA +红藻氨酸处理的耳蜗中的轴突的数量。此外，在用Y-27632处理的耳蜗中，螺旋神经节和内毛细胞之间的突触显著增加。这项研究的结果表明，ROCK抑制可能是一种潜在的策略，在螺旋神经节的外周轴突再生和突触形成的内毛细胞的耳蜗，持续兴奋毒性损伤，这是内耳疾病的主要病因之一。
In the past, most inner ear diseases were thought to start with the impairment of the sensory epithelium of the cochlea before subsequently progressing to secondary neural degeneration. However, recent studies show that loss of primary synapses accompanied by excitotoxic degeneration of peripheral axons is likely to be the underlying pathology in sensorineural hearing loss. Rho-associated coiled-coil containing protein kinase (ROCK) inhibition has been reported to have neuroprotective and regenerative effects on synaptic pathways. Therefore, we analyzed the effect of ROCK inhibition using Y-27632 in a model of peripheral axonal damage in the spiral ganglion neurons created using the glutamate agonists, N-methyl-D-aspartate (NMDA) and kainic acid, to induce excitotoxic trauma in the explanted cochlea. The number of axons projecting to hair cells in the cochlea treated with Y-27632 was significantly greater than those in the cochlea treated only with NMDA + kainic acid. Furthermore, there was a significant increase in synapses between the spiral ganglion and the inner hair cells in the cochlea treated with Y-27632. The findings of this study suggest that ROCK inhibition could be a potential strategy for the regeneration of peripheral axons in the spiral ganglion and synapse formation in the inner hair cells of a cochlea that has sustained excitotoxic injury, which is one of the primary etiologies of inner ear disease.
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影响因子：
1.1
作者：
Menorca RM;Fussell TS;Elfar JC
通讯作者：
Elfar JC
影响因子：
2.8
作者：
Bodmer, D;Brors, D;Ryan, AF
通讯作者：
Ryan, AF
影响因子：
16.6
作者：
Defourny, Jean;Poirrier, Anne-Lise;Malgrange, Brigitte
通讯作者：
Malgrange, Brigitte
影响因子：
3.3
作者：
Lie, M.;Grover, M.;Whitlon, D. S.
通讯作者：
Whitlon, D. S.
影响因子：
5.3
作者：
MUNEMITSU, S;INNIS, MA;POLAKIS, P
通讯作者：
POLAKIS, P