Y-27632, a ROCK inhibitor, improved laser-induced shock wave (LISW)-induced cochlear synaptopathy in mice.
Y-27632, a ROCK inhibitor, improved laser-induced shock wave (LISW)-induced cochlear synaptopathy in mice.
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DOI：
10.1186/s13041-021-00819-1
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发表时间：
2021-07-03
期刊：
影响因子：
3.6
通讯作者：
Kakehata S
中科院分区：
文献类型：
--
作者：
Koizumi Y;Mizutari K;Kawauchi S;Sato S;Shiotani A;Kakehata S
最近，一种被称为耳蜗突触病的病理状态已经被阐明，并且作为在毛细胞衰竭之前发生的听觉神经突触的障碍，它已经被认为是感音神经性听力损失的主要原因。然而，耳蜗突触病是无法治疗的。据报道，抑制rho相关卷曲螺旋蛋白激酶（ROCK）（一种丝氨酸-苏氨酸蛋白激酶）对神经系统（包括内耳）中的突触通路具有神经保护和再生作用。我们先前证明了ROCK抑制剂Y-27632对体外兴奋毒性耳蜗神经损伤模型的再生作用。在本研究中，我们的目的是验证ROCK抑制对激光诱导冲击波（LISW）诱导的耳蜗突触病小鼠体内的影响。在确认受损耳蜗中ROCK 1/2表达升高后，我们通过中耳局部施用Y-27632。Y-27632处理的耳蜗中听性脑干反应的I波振幅和突触数量显著增加。这些结果清楚地表明，ROCK抑制在耳蜗突触病的治疗中具有有希望的临床应用，耳蜗突触病是感音神经性听力损失的主要病理。
Recently, a pathological condition called cochlear synaptopathy has been clarified, and as a disorder of the auditory nerve synapses that occurs prior to failure of hair cells, it has been recognized as a major cause of sensorineural hearing loss. However, cochlear synaptopathy is untreatable. Inhibition of rho-associated coiled-coil containing protein kinase (ROCK), a serine-threonine protein kinase, has been reported to have neuroprotective and regenerative effects on synaptic pathways in the nervous system, including those in the inner ear. We previously demonstrated the regenerative effect of the ROCK inhibitor, Y-27632, on an excitotoxic cochlear nerve damage model in vitro. In this study, we aimed to validate the effect of ROCK inhibition on mice with cochlear synaptopathy induced by laser-induced shock wave (LISW) in vivo. After the elevation of ROCK1/2 expression in the damaged cochlea was confirmed, we administered Y-27632 locally via the middle ear. The amplitude of wave I in the auditory brainstem response and the number of synapses in the Y-27632-treated cochlea increased significantly. These results clearly demonstrate that ROCK inhibition has a promising clinical application in the treatment of cochlear synaptopathy, which is the major pathology of sensorineural hearing loss.
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影响因子：
16.2
作者：
Mizutari K;Fujioka M;Hosoya M;Bramhall N;Okano HJ;Okano H;Edge AS
通讯作者：
Edge AS
影响因子：
5.3
作者：
Koizumi Y;Ito T;Mizutari K;Kakehata S
通讯作者：
Kakehata S
影响因子：
2.9
作者：
Amano, Mutsuki;Nakayama, Masanori;Kaibuchi, Kozo
通讯作者：
Kaibuchi, Kozo
影响因子：
16.2
作者：
IP, NY;STITT, TN;YANCOPOULOS, GD
通讯作者：
YANCOPOULOS, GD
影响因子：
16.6
作者：
Defourny, Jean;Poirrier, Anne-Lise;Malgrange, Brigitte
通讯作者：
Malgrange, Brigitte