Regenerative Effect of a ROCK Inhibitor, Y-27632, on Excitotoxic Trauma in an Organotypic Culture of the Cochlea

Frontiers in Cellular Neuroscience

Tsukasa Ito¹  Yutaka Koizumi¹  Seiji Kakehata¹  Kunio Mizutari² 

[1] Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Yamagata University, Yamagata, Japan;Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College, Saitama, Japan;

关键词: cochlea;    spiral ganglion;    Y-27632;    hearing loss;    inner ear;    synapse;   

DOI  :  10.3389/fncel.2020.572434

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown