Regenerative effect of a ROCK Inhibitor, Y-27632, on excitotoxic trauma in an organotypic culture of the cochlea

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K16887
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Yamagata University
• Principal Investigator: Koizumi Yutaka 山形大学, 医学部, 非常勤講師 (80723585)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 内耳 / 感音難聴 / 聴神経 / シナプス / ROCK阻害薬 / 蝸牛 / 再生 / 器官培養

Outline of Final Research Achievements

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 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.

Free Research Field

内耳基礎研究

Academic Significance and Societal Importance of the Research Achievements

近年になりprimary neural degenerationという概念が提唱され、感音難聴の成因として聴神経の障害が注目を集めている。本研究では内耳蝸牛の器官培養系を用いて、神経保護効果および神経・シナプス再生作用を有するとされるROCK阻害薬の聴神経障害への効果について検討した。ROCK阻害薬はすでに臨床応用されている薬剤であり、内耳領域でも効果が確認できれば、比較的簡便で画期的な聴覚障害の治療法となる可能性がある。今後、蝸牛聴神経でのRhoA/ROCK経路の発現変化についての解析および、in vivoでのROCK阻害薬の効果についてさらなる検討が期待される。