Reactive oxygen species; physiological role in the brain
| Project/Area Number |
19K22834
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
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| Research Institution | Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology |
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Principal Investigator |
Endo Shogo 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (60192514)
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| Co-Investigator(Kenkyū-buntansha) |
柿澤 昌 京都大学, 薬学研究科, 准教授 (40291059)
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| Project Period (FY) |
2019-06-28 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | ROS / 8-nitro-cGMP / 小脳 / 運動記憶 / 神経可塑性 / LTP/LTD / NO / 活性酸素種 / 記憶 / プルキンエ細胞 / cGMP / 一酸化窒素 |
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| Outline of Research at the Start |
スポーツや日常の活動に伴い発生する活性酸素種は、生体分子の酸化修飾を介してガン化、細胞死、老化を招く「悪玉」であるとされている。一方で、生体は活性酸素種を積極的に産生する酵素を有しており、活性酸素種が何らかの生理的な役割を担うことが考えられる。そこで本研究では、活性酸素種の「善玉」としての役割に着目し、特に小脳を介した運動記憶および神経可塑性への活性酸素種の関与を解明する。
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| Outline of Final Research Achievements |
Reactive Oxygen Species (ROS) damages DNA and proteins through their chemical modifications. Because these lead to cell death, cancer and aging-related physiological issues in our body, ROS is thought to be “harmful molecule” in our common knowledge. On the other hand, recent studies suggest ROS plays physiological roles in cells and tissues. In this study, using biochemical and electrophysiological techniques, and behavioral and imaging analyses, we examined ROS's roles in cerebellum and found followings; 1) ROS generated by physiological patterns of neuronal activities; 2) ROS is involved in cerebellum-dependent motor memory and neuronal plasticity; 3) ROS-8-nitro-cGMP pathway affects the neuronal plasticity direction in a calcium-dependent manner in Purkinje cells. The results indicate that ROS is “physiological messenger” and is involved in higher brain functions. Future studies may clarify mechanism of ROS production and ROS-dependent long-term memory based on this study.
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| Academic Significance and Societal Importance of the Research Achievements |
抗酸化物質（ビタミンC やEなど）は、ROSが招く老化やガンなどの悪玉作用を抑制するとして抗加齢や健康増進のために補助食品として広く一般に用いられている。一方で、通常の食事を摂ればこの様な補助食品は不要であるとも報告されている。本研究では、脳においてROSが神経可塑性、運動記憶に重要であることを示した。そして、過剰なビタミンC／EやROSを除去する物質の投与が可塑性や記憶を阻害することも示した。したがって、ROSは必ずしも除去すれば良いわけでは無く、抗酸化物質の利用や過剰摂取に注意を要することが考えられる。
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Report
(3 results)
Research Products
(39 results)
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[Journal Article] Apelin2021
Author(s)
Kakizawa S
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Journal Title
Handbook of Hormones (2nd Ed.)" (eds Ando H, Ukena K, Nagata S). Elsevier (Tokyo)
Volume: 2
Related Report
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[Journal Article] TRPM7 channels mediate spontaneous Ca2+ fluctuations in growth plate chondrocytes that promote bone development.2019
Author(s)
Qian N, Ichimura A, Takei D, Sakaguchi R, Kitani A, Nagaoka R, Tomizawa M, Miyazaki Y, Miyachi H, Numata T, Kakizawa S, Nishi M, Mori Y, Takeshima H.
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Journal Title
Science signaling
Volume: 12
Issue: 576
Pages: 4847-4847
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Construction and integration of the All-in-One type single double-conditional shRNA expression vectors for spatio-temporal gene and/or cell targeting2019
Author(s)
Oyamada H, Ao Y, Kudo Y, Matsuoka T, Okamoto R, Murayama T, Yamazawa T, Kakizawa S, Oguchi T, Kimura A, Yasumoto T, Mori Y, Tsuji M, Oguchi K, Kiuchi Y
Organizer
NEURO2019 第42回日本神経科学大会
Related Report
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[Presentation] Amelioration of potentially harmful oxidative and nitrosative protein modifications by regular exercise in aged animals: A molecular mechanism of the beneficial effects2019
Author(s)
Sataro Goto, Shuo-wen Chang, Shohei Shinozaki, Shuichi Yanai, Hideko Nakamoto, Ayako Matsumoto, Hisashi Naito, Hiroyuki Kobayshi, Masao Kaneki, Shogo Endo, & Zsolt Radak
Organizer
11th International Association of Gerontology and Geriatrics Asia/Oceania Regional Congress
Related Report
Int'l Joint Research
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