| Project/Area Number |
17K16887
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Yamagata University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| 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 / cochlear synaptopathy / 聴覚再生 / 再生医学 / 感音性難聴 |
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| 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.
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| 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。
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