Pathophysiological study of age-related hearing loss by glutamate imaging
| Project/Area Number |
16K11204
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | National Rehabilitation Center for Persons with Disabilities |
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Principal Investigator |
Takago Hideki 国立障害者リハビリテーションセンター(研究所), 研究所 感覚機能系障害研究部, 研究室長 (70401354)
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| Co-Investigator(Kenkyū-buntansha) |
大島 知子 東京大学, 大学院医学系研究科(医学部), 特任研究員 (50731783)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 内耳 / 蝸牛 / 有毛細胞 / シナプス / リボン / グルタミン酸 / イメージング / パッチクランプ / リボンシナプス / グルタミン酸イメージング / 加齢性難聴 / 聴覚 / 蝸牛神経 |
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| Outline of Final Research Achievements |
This study aims to clarify pathophysiological mechanisms for age-related hearing loss (ARHL) using patch-clamp and glutamate imaging techniques to analyze senescent changes in inner hair cell (IHC) ribbon synapse functions of C57BL/6J mice, which are routinely employed as a model for ARHL. Whole-cell patch-clamp recordings from IHCs revealed smaller Ca2+ current amplitude in ARHL-model mice than in normal-hearing young mice. Notably, glutamate imaging using a glutamate optical sensor named EOS visualized excitatory neurotransmitter release from IHCs in young mice in real-time, although its temporal resolution remains to be improved to monitor auditory signal transduction in a millisecond time scale. This novel imaging technique might be a useful tool for analyses of synaptic functions of deaf mutant mice as well as differential diagnosis of patients with sensorineural hearing loss using disease-specific hair cell-like iPS cells.
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| Academic Significance and Societal Importance of the Research Achievements |
グルタミン酸イメージングを活用した本研究により、マウス蝸牛・内有毛細胞において神経伝達物質放出をリアルタイムで計測する道が拓かれた。今後、グルタミン酸イメージングの時間分解能を改善するとともに適用標本を拡大することで、感音難聴の病態解明研究が進展することが期待される。また、疾患特異的有毛細胞様iPS細胞を活用することで、感音難聴患者・児の障害部位の診断が現状よりも正確に行えるようになる可能性がある。
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Report
(5 results)
Research Products
(16 results)
