| Project/Area Number |
16K08196
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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 |
Physical pharmacy
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| Research Institution | Kyushu University |
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Principal Investigator |
Yamato Mayumi 九州大学, 薬学研究院, 学術研究員 (30380695)
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| Project Period (FY) |
2016-10-21 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 脳機能 / 酸化ストレス / 腎不全 / 尿毒素 / 脳障害 / 尿毒症物質 / 腎症モデル / 認知症 / 生活習慣病 |
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| Outline of Final Research Achievements |
Accumlating evidence have suggested that kidney failure links dementia. However, the underlying mechanism remains unclear. Here we show uremic toxin and free radicals involvement in brain damage in a kidney failure animal model.
For the induction of kidney failure in mice, C57/BL-6 animals were fed with a 0.25% adenine-containing diet during a period of 6 weeks. It has been reported that guanidinosuccinic acid (GSA), which is one of urinary toxins, transfers to the brain and causes neurological symptoms such as epilepsy. In adenine-supplemented mice, GSA was also elevated in the blood and brain of mice. Furthermore, in the disease model mice, a decrease in pyramidal cell number was observed in the hippocampus CA3 region, and a significant decrease in cognitive function was confirmed in the radial water maze test.
These results suggested that in the adenine-supplemented mice, the uremic toxin GSA produced by renal injury causes cognitive decline.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、膵臓の病気である糖尿病においては、合併症である腎症からさらには慢性腎不全に移行し、透析が必要となる患者の数が急増する等の問題が生じている。通常、腎臓、脳等の臓器間には密接かつ精巧な機能的連関があり、生体内恒常性が維持されている。しかし、疾患発症時においては、この連関が仇となり合併症を引き起こすものと考えられる。疾患時における他の臓器に与える影響を解明し、負の連関を選択的に断ち切ることは、合併症の予防につながり、さらには合併症治療薬開発等の創薬への応用展開へ重要な役割を果たすものと期待される。
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