Analysis of RhoA/Rho-kinase signals in neuronal circuit
Project/Area Number |
18K14816
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 46010:Neuroscience-general-related
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Research Institution | Nagoya University |
Principal Investigator |
KURODA Keisuke 名古屋大学, 医学系研究科, 特任准教授 (80631431)
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Project Period (FY) |
2018-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | シグナル伝達機構 / 神経科学 / Rho kinase / RhoA / 神経回路 / シナプス / 行動解析 / 細胞種特異的 / 細胞腫特異的 / 神経化学 / 細胞内情報伝達 / シグナル解析 / Rho-kinase / アデノ随伴ウイルス / 側坐核 |
Outline of Final Research Achievements |
We analyzed the intracellular signaling of RhoA, a Rho family low molecular weight G protein, and its downstream molecule, Rho-kinase, in neurons. We found that the activator (GEF) and inactivator (GAP) of RhoA were phosphorylated in a neural activity-dependent manner. We observed changes in synaptic morphology and behavior in mice injected with AAV, which regulates the activity of RhoA and Rho-kinase, and in double-conditional knockout mice of Rho-kinase (Rock1 and Rock2). These findings suggest that neurons regulate synaptic morphology and behavior via RhoA and Rho-kinase signaling.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では細胞種特異的にCreを発現するトランスジェニック(Tg)マウスやアデノ随伴ウイルス(AAV)を組み合わせ、特にRhoファミリー低分子量G蛋白質RhoAおよびその下流分子であるRho-kinaseシグナルについて個体内での細胞内シグナル伝達を解析し、その生理機能を明らかにした。研究代表者の参加する研究グループでは、ARHGAP10というRhoAのGAPが新たな統合失調症リスク遺伝子であること、Rhoシグナルが統合失調症治療の有望な創薬ターゲットであることを報告している。これらの成果から、精神疾患の病態解明や新たな治療法の開発に繋がることが期待される。
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Report
(5 results)
Research Products
(15 results)
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[Journal Article] Accumbal D2R-medium spiny neurons regulate aversive behaviors through PKA-Rap1 pathway.2020
Author(s)
Lin, Y-H., Yamahashi, Y., Kuroda, K., Faruk M. O., Zhang, X., Yamada, K., Yamanaka, A., Nagai, T., Kaibuchi, K.
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Journal Title
Neurocham. Int.
Volume: 143
Pages: 104935-104935
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Balance between dopamine and adenosine signals regulates the PKA/Rap1 pathway in striatal medium spiny neurons2018
Author(s)
Zhang XJ, Nagai T, Ahammad RU, Kuroda K, Nakamuta S, Nakano T, Yukinawa N, Funahashi Y, Yamahashi Y, Amano M, Yoshimoto J, Yamada K, and Kaibuchi K.
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Journal Title
Neurochemistry International
Volume: 122
Pages: 8-18
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Phosphorylation of Npas4 by MAPK regulates reward-related gene expression and behaviors2019
Author(s)
Yasuhiro Funahashi, Anthony Ariza, Ryosuke Emi, Yifan Xu, Shan Wei, Ko Suzuki, Sachi Kozawa, Tetsuya Takano, Yoshimitsu Yura, Keisuke Kuroda, Taku Nagai, Mutsuki Amano, Kiyofumi Yamada, Kozo Kaibuchi
Organizer
第42回日本神経科学学会・ 第62回日本神経化学会大会合同大会
Related Report
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