Development of a revolutionary and inventive therapeutic drug for intractable brain diseases, targeting GIRK channel
| Project/Area Number |
26460114
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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 |
Pharmacology in pharmacy
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| Research Institution | Kumamoto Health Science University |
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Principal Investigator |
Kazuo Takahama 熊本保健科学大学, 保健科学部, 教授 (80150548)
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| Co-Investigator(Kenkyū-buntansha) |
副田 二三夫 第一薬科大学, 薬学部, 准教授 (10336216)
三隅 将吾 熊本大学, 大学院生命科学研究部(薬), 教授 (40264311)
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| Co-Investigator(Renkei-kenkyūsha) |
YAMAMURA Kenichi 熊本大学, 発生医学研究所, 教授 (90115197)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | ＧＩＲＫ ｃｈａｎｎｅｌ / ＧＩＲＫ２ ｓｕｂｕｎｉｔ / CRISPR/Cas system / Ｋｎｏｃｋｏｕｔ ｍｏｕｓｅ / ｖｅｎｔｒａｌ ｔｅｇｍｅｎｔａｌ ａｒｅａ / ｄｏｐａｍｉｎｅ ｎｅｕｒｏｎ / ａｎｔｉｄｅｐｒｅｓｓａｎｔ ｅｆｆｅｃｔ / ｔｉｐｅｐｉｄｉｎｅ / GIRKチャネル / 遺伝子改変マウス / 腹側被蓋野 / 側坐核 / ドパミンニューロン / ドパミントランスポーター / 抗うつ様作用 / チペピジン / 新奇物体認識試験 / 5-HT1A受容体 / 5-HT7受容体 / ドパミン / 前頭皮質 / ドパミンD2 レセプター / うつ病 / GIRK2KOマウス / 認知症改善作用 / アルツハイマー病 / ドパミン D1 レセプター / ケタミン / コンデイショナルGIRK2KOマウス， |
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| Outline of Final Research Achievements |
Using the CRISPR/Cas system, conditional knockout mice in which GIRK2 subunit was deleted in the neurons expressing dopamine transporter were generated. Histochemical and electrophysiological analysis of the ventral tegmental area (VTA) in this mouse revealed that GIRK2 subunit was deleted in the neurons expressing DAT and its electrophysiological function of the GIRK channels is deteriorated in this neurons. In the forced swimming test, this KO mice showed a significant decrease in the immobility time without little affecting general behaviors such as locomotion. The present results further support our hypothesis that activation of the dopamine neurons via inhibition of GIRK channels in the VTA may be involved in the expression of antidepressant-like effect of centrally acting antitussives such as tipepidine.
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Report
(5 results)
Research Products
(27 results)
