2022 Fiscal Year Final Research Report
Regulation of brain functions by reactive oxygen species-mediated signal
| Project/Area Number |
19K06955
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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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| Review Section |
Basic Section 46030:Function of nervous system-related
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| Research Institution | Kyoto University |
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Principal Investigator |
Kakizawa Sho 京都大学, 薬学研究科, 准教授 (40291059)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | reactive oxygen species / long-term memory / motor learning / synaptic plasticity / cerebellum / nitric oxide / long-term depression / mouse |
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| Outline of Final Research Achievements |
Involvement of reactive oxygen species (ROS)-mediated signals in cerebellar-dependent motor learning and the underlying cerebellar synaptic plasticity, long-term depression (LTD), was examined, because ROS induces its effects on the target molecules through stable chemical modification(s). Optokinetic response (OKR), a kind of cerebellar-dependent motor learning, was impaired when inhibitor of ROS or ROS synthase was applied to the cerebellum. Cerebellar LTD was also abolished by the inhibitors. As the downstream signals, involvements of 8-nitro-cGMP in OKR and cerebellar LTD were also demonstrated. In addition, imaging study using fluorescent probe for ROS revealed that ROS was produced by neuronal stimulation inducing cerebellar LTD, suggesting involvement of endogenous ROS in the motor learning and cerebellar LTD. Taken together, essential roles of endogenous ROS - 8-nitro-cGMP signaling in long-term memory of motor learning and cerebellar synaptic plasticity were indicated.
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| Free Research Field |
神経生理学、神経薬理学、基礎老化学
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| Academic Significance and Societal Importance of the Research Achievements |
活性酸素(reactive oxygen species; ROS)は、従来、老化や生活習慣病の原因となる、いわゆる悪玉因子として生体に作用すると考えられてきた。本研究では、ROSが、その下流となる8-nitro-cGMPを介して、小脳依存的な運動学習およびその基盤となる小脳シナプス可塑性の一種、長期抑圧(long-term depression; LTD)に関与することが示された。このことはROSは脳の高次機能の発現に必要な生理的因子であることを示唆するものであり、本成果により、これまで悪玉因子とされてきたROSが生理的シグナルでもあるというパラダイムシフトがもたらされることが期待される。
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