2021 Fiscal Year Final Research Report
Elucidating the pathogenic mechanism of CKD-associated cognitive dysfunction and muscle wasting as revealed by metabolic changes in organs
Project/Area Number |
19K08669
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53040:Nephrology-related
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Research Institution | Tohoku University |
Principal Investigator |
Sato Emiko 東北大学, 薬学研究科, 准教授 (20466543)
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Co-Investigator(Kenkyū-buntansha) |
高橋 信行 東北大学, 薬学研究科, 教授 (40588456)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | ウレミックサルコペニア / 認知機能障害 / 尿毒素 |
Outline of Final Research Achievements |
Chronic kidney disease (CKD)-associated cognitive dysfunction and muscle wasting are important problems with the aging of the patients with CKD. In this study, we elucidated the pathogenesis of CKD-associated cognitive dysfunction and muscle wasting using cell line and animal disease model. We first evaluated the effects of various uremic toxins on the mouse myoblast cell line C2C12 and the mouse hippocampal neuronal cell line HT-22. We found that indoxyl sulfate and indole negatively affected the hippocampal neuronal cell line, and that methylglyoxal induced intracellular metabolic changes and decreased ATP production in only myoblasts. Furthermore, we found that intracellular metabolic changes are also induced in the kidney in CKD model mouse, and that nicotinamide treatment protect the progression of the CKD dysfunction.
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Free Research Field |
臨床薬学
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Academic Significance and Societal Importance of the Research Achievements |
CKDでは本来体外へと排泄すべき尿毒素が体内に蓄積し、この尿毒素蓄積は腎臓や心臓に悪影響を及ぼし心血管疾患を増加させる。尿毒素蓄積は骨代謝異常、腎性貧血など種々のCKD関連合併症にも関与するが、尿毒素蓄積が認知機能低下・筋消耗にどのように関与しているかはいまだ不明な点が多い。本研究は尿毒素蓄積が海馬神経細胞株および筋芽細胞株に悪影響を及ぼすこと、またその機序を明らかにした。CKD関連-認知機能障害・筋消耗の発症進展に関与する機序の解明は、それに基づいた治療法の開発が可能となる
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