Mechanisms of both cognitive deficits and behavioral and psychological symptoms of Alzheimer's disease in KATP channel mutant mice
| Project/Area Number |
18K06887
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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 48030:Pharmacology-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | アルツハイマー病 / 認知機能障害 / KATPチャネル / 精神機能障害 / 病態解明 / 中核・周辺症状 / 不安様症状 / 扁桃体 / カルシウムシグナル / 記憶学習 / うつ症状 / 不安症状 / 遺伝子欠損マウス / メマンチン / ADの中核症状 / AD周辺症状 |
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| Outline of Final Research Achievements |
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by both cognitive deficits and behavioral and psychological symptoms of dementia (BPSD). Here, we demonstrated that mutant mice in Kir6.2 channel observed both cognitive deficits and aggressive behaviors. By contrast, mutant mice in Kir6.1 channel observed anxiety-like behaviors, depressive-like behaviors and aggressive behaviors. In this study, we performed that detection of brain region at behavioral phenotypes and mechanisms of intracellular signaling, therefore, we detected psychological role of KATP channel in both cognitive deficits and BPSD of AD.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の目的は、KATP（Kir6.1/Kir6.2）チャネルを標的とした「ADの脳糖尿病仮説」の実証である。申請者はADモデルマウスにおいて海馬および大脳皮質におけるKir6.1/Kir6.2チャネルのタンパクおよびmRNA発現量が有意に低下していることを同定した。この結果は、「ADの脳糖尿病仮説」においてKATPチャネルの発現量の低下、すなわちKATPチャネルの機能低下がADの中核・周辺症状に関与する可能性を示唆するものであり、本研究で実施するKATPチャネル欠損マウスの表現型解析（AD中核・周辺症状の同定）は学術的独自性と創造性が極めて高い研究課題と考えられる。
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Reduced expression of Na+/Ca2+ exchanges is associated with cognitive deficits seen in Alzheimer’s disease model mice.2018
Author(s)
Shigeki Moriguchi, Satomi Kita, Masahiro Fukaya, Makoto Osanai, Ryo Inagaki, Yuzuru Sasaki, Hisanao Izumi, Kyoji Horie, Junji Takeda, Takashi Saito, Hiroyuki Sakagami, Takaomi C Saido, Takahiro Iwamoto and Kohji Fukunaga
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Journal Title
Neuropharmacology
Volume: 131
Pages: 291-303
Related Report
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