Mechanism of progression of dementia and sarcopenia through gut-brain-muscle linkage mediated by monocytes and microglia
| Project/Area Number |
18K19769
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
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| Research Institution | Department of Clinical Research, National Hospital Organization Kyoto Medical Center |
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Principal Investigator |
Satoh-Asahara Noriko 独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 研究部長 (80373512)
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| Co-Investigator(Kenkyū-buntansha) |
菅波 孝祥 名古屋大学, 環境医学研究所, 教授 (50343752)
小谷 和彦 自治医科大学, 医学部, 教授 (60335510)
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| Project Period (FY) |
2018-06-29 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 単級極性 / ミクログリア / 腸内細菌叢 / 認知機能 / サルコペニア / 臓器連関 / 腸脳筋連関 / 単球極性 / 腸ー脳ー筋連関 / 腸-脳-筋連関 / 単球機能 / 認知症 / 生活習慣病 / 単球・ミクログリア |
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| Outline of Final Research Achievements |
We recognized the deterioration of intestinal microflora function and chronic inflammation, which is a risk for dementia and sarcopenia, in diabetic patients. In this study, we examined the pathogenesis of dementia and sarcopenia (gut-brain-muscle linkage) due to pathological interactions with the brain and muscle starting from the deterioration of the intestinal environment. In particular, we focused on function of monocyte/macrophage/microglia (M1/M2 polarity, TREM2) as a player of the pathological linkage, and found that serum sTREM2 is a predictive indicator of dementia and brain inflammation in the general population, diabetes mellitus and obese diabetic model mice. We generated TREM2-deficient mice to elucidate the mechanism of progression. In addition, we have clarified the effects of administration of diabetic drugs and flavonoids on the gut-brain-muscle interaction to establish optimal prophylaxis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では糖尿病・肥満患者において慢性炎症、特に免疫担当細胞である単球・マクロファージ極性（M1/M極性・TREM2発現）異常を基盤に病的な腸-脳-筋連関が生じ、認知症やサルコペニアが発症・進展する可能性が示唆された。本研究の成果は、加齢・代謝性疾患にて悪化する腸-脳-筋連関の包括的な予知バイオマーカーや予防法の確立に繋がり、超高齢社会の本邦で増加し問題となる生活習慣病に伴う認知症・サルコペニアに対する包括的・革新的先制医療の実現や健康寿命延伸に寄与でき、本邦の医療と福祉に多大な波及効果と貢献が期待できる。
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Report
(5 results)
Research Products
(45 results)
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[Journal Article] Role of serum myostatin in the association between hyperinsulinemia and muscle atrophy in Japanese obese patients.2018
Author(s)
Tanaka M, Masuda S, Yamakage H, Inoue T, Ohue-Kitano R, Yokota S, Kusakabe T, Wada H, Sanada K, Ishii K, Hasegawa K, Shimatsu A, Satoh-Asahara N.
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Journal Title
Diabetes Res Clin Pract.
Volume: 142
Pages: 195-202
DOI
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Peer Reviewed / Open Access
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[Presentation] 肥満・糖尿病における新規認知症予知指標・TREM2の病態意義 ―国立病院機構多施設共同研究―2018
Author(s)
17)浅原哲子, 田中将志, 山陰一, 井上隆之, 北野隆司, 村中和哉, 荒木里香, 的場ゆか, 齋藤美穂, 栗田征一郎, 米澤一也, 田中剛史, 鈴木雅裕, 澤村守夫, 西村元伸, 小鳥真司, 日下部徹, 島津章
Organizer
第91回日本内分泌学会学術集会
Related Report
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