How anti-Alzheimer's drug affect microglia and neurovascular unit ?
| Project/Area Number |
17K10275
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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 |
Psychiatric science
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| Research Institution | Saga University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
門司 晃 佐賀大学, 医学部, 教授 (00294942)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ミクログリア / アルツハイマー型認知症 / 認知症治療薬 / ドネペジル / カルシウム / 貪食能 / アミロイドβ / 脳血管内皮細胞 / 細胞内カルシウムイオン動態 / ＮＯ / 薬理学 / 神経科学 / 医学 |
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| Outline of Final Research Achievements |
Microglia are resident innate immune cells which release many factors including proinflammatory cytokines when they are activated. As one of underlying mechanisms of Alzheimer's disease (AD), dysregulation of intracellular Ca2+ homeostasis has also been proposed as a common cause of neural dysfunction. Donepezil, one of acetylcholinesterase (AChE) inhibitors, is clinically used for the treatment of AD. The major mechanism of donepezil’s effects is to inhibit neuronal AChE activity. We examined whether pretreatment with donepezil affects the intracellular Ca2+ mobilization and phagocytic activity in rodent microglial cells. We observed that pretreatment with donepezil promoted phagocytic activity of mouse primary microglial cells.These suggest that donepezil could directly modulate the microglial function in vitro and might favor the shift of microglial cells from a pro-inflammatory to a more neuroprotective phenotype in the rodent brain.
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| Academic Significance and Societal Importance of the Research Achievements |
高齢化社会は今後も続き多数の認知症高齢者に認知症治療薬が処方されていくと考えられるが認知症治療薬がニューロン以外の細胞に及ぼす作用および細胞内メカニズムについて驚くほど知見が不足しているのが現状である。本研究課題の遂行によりニューロンーグリアー脳血管系の老化を背景とした認知症の病態解明および治療薬開発に繋がる新たな知見を得られる可能性が高いと考える。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] ATP and Repetitive Electric Stimulation Increases Leukemia Inhibitory Factor Expression in Astrocytes: A Potential Role for Astrocytes in the Action Mechanism of Electroconvulsive Therapy2020
Author(s)
Maruyama S, Boku S, Okazaki S, Kikuyama H, Mizoguchi Y, Monji A, Otsuka I, Sora I, Kanazawa T, Hishimoto A, Yoneda H.
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Journal Title
Psychiatry Clin Neurosci .
Volume: .
Issue: 5
Pages: 12986-12986
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Serum Oxytocin Levels and Logical Memory in Older People in Rural Japan2020
Author(s)
Yutaka Kunitake, Yoshiomi Imamura, Yoshito Mizoguchi, Jun Matsushima, Hiroshi Tateishi, Toru Murakawa-Hirachi, Hiromi Nabeta, Toshiro Kawashima, Naoki Kojima, Shigeto Yamada, Akira Monj
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Journal Title
Journal of Geriatric Psychiatry and Neurology
Volume: -
Issue: 2
Pages: 156-161
DOI
Related Report
Peer Reviewed
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[Journal Article] Improvement of frontal lobe dysfunction and white matter integrity by rTMS in treatment-resistant depression2019
Author(s)
Tateishi H, Nishihara M, Kawaguchi A, Matsushima J, Murakawa T, Haraguchi Y, Kunitake Y, Maekawa T, Kato TA, Asami T, Mizoguchi Y, Monji A
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Journal Title
Neuropsychiatric Disease and Treatment
Volume: 15
Pages: 3079-3079
DOI
Related Report
Peer Reviewed
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[Journal Article] Oxytocin levels and sex differences in autism spectrum disorder with severe intellectual disabilities.2018
Author(s)
Aita C, Mizoguchi Y, Yamamoto M, SeguchI Y, Yatsuga C, Nishimura T, Sugimoto Y, Takahashi D, Nishihara R, Ueno T, Nakayama M, Kuroki T, Nabeta H, Imamura Y, Monji A.
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Journal Title
Psychiatry Res.
Volume: 273
Pages: 67-74
Related Report
Peer Reviewed
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