Actin-based model of synaptic plasticity
| Project/Area Number |
17H03557
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Gunma University |
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Principal Investigator |
Shirao Tomoaki 群馬大学, 大学院医学系研究科, 教授 (20171043)
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| Co-Investigator(Kenkyū-buntansha) |
花村 健次 群馬大学, 大学院医学系研究科, 准教授 (40361365)
山崎 博幸 群馬大学, 大学院医学系研究科, 助教 (10334137)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
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| Keywords | アクチン / ドレブリン / シナプス / アルツハイマー病 / 培養 / 超微小形態 / ライブイメージング / アクチン細胞骨格 / コフィリン / 海馬 / 超解像顕微鏡 / スパイン / 分子動態解析 / シナプス可塑性 / 動態 / アクチン線維 / PSD-95 / 神経細胞培養 / 超解像顕微鏡観察 / 生体に光子顕微鏡観察 |
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| Outline of Final Research Achievements |
We succeeded in improving the reproducibility of the experiment by using the same lot of cryopreserved dissociated neurons for each experiment. Microscopic localization of drebrin, PSD-95, and CaMKII in spine was analyzed by super resolution microscopy using bunker method, and their glutamate-stimulated change in the localization within the dendritic spine. Furthermore, we compared the morphological dynamic changes of spines in between drebrin A-specific knockout mice (DAKO) and wild type mice. In addition, we analyzed the relationship between the stabilized actin filaments bound to drebrin and the dynamics of CaMKII, and clarified that the stability of actin filaments is involved in the dynamics of CaMKII.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果により、ドレブリンの結合により作り出される安定化アクチン繊維の有無によりスパインの形態変化やスパイン内の機能タンパク質の動態が制御されていることがわかった。この結論から、アルツハイマー病におけるドレブリンの消失がシナプスの全般的機能不全を引き起こし、認知症の発症に深く関連していることが示唆された。ドレブリンの消失を防ぐことにより、将来的に認知症の治療薬を開発できる可能性を強く示唆しており、高齢化社会の到来後も生活の質を保った持続可能な社会を作ることに貢献すると考えられる。
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Report
(3 results)
Research Products
(64 results)
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[Journal Article] Drebrin restricts rotavirus entry by inhibiting dynamin-mediated endocytosis2017
Author(s)
Li B, Ding S, Feng N, Mooney N, Ooi YS, Renf L, Diep J, Kelly MR, Yasukawa LL, Patton JT, Yamazaki H, Shirao T, Jackson PK, Greenberg HB
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Journal Title
Proc Natl Acad Sci U S A,
Volume: -
Issue: 18
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The role of drebrinin neurons2017
Author(s)
Shirao T, Hanamura K, Koganezawa N, Ishizuka Y, Yamazaki H, Sekino Y.
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Journal Title
J. Neurochem.
Volume: -
Issue: 6
Pages: 819-834
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Radiation effects on neurons and its consequences: investigation by in vitro, in vivo and in silico studies2018
Author(s)
Anggraeini Puspitasari, Hiroyuki Yamazaki, Noriko Koganezawa, Nobuhiko Kojima, Hidemasa Kawamura, Aimee Louise McNamara, Jan P Schuemann, Harald Paganetti, Tomoaki Shirao, Takashi Nakano, Kathryn D Held
Organizer
The 3rd Meeting of Federati on of Asian Organizations for Radiation Oncology
Related Report
Int'l Joint Research
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