Pathological role of endoplasmic reticulum stress in the hippocampal dysfunction seen in chronic kidney disease
| Project/Area Number |
17K08965
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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 |
Applied pharmacology
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| Research Institution | Nihon University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
三枝 禎 日本大学, 松戸歯学部, 教授 (50277456)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 慢性腎臓病 / 海馬 / 記憶 / 尿毒素 / 小胞体ストレス / 腎機能 / 腎線維化 / 植物エキス / S-allyl-L-cysteine / 小胞体ストレス抑制 / 慢性腎不全 / 酸化ストレス / 痴呆 / 薬理学 / トランスレーショナルリサーチ |
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| Outline of Final Research Achievements |
Cognitive dysfunction is a known complication of chronic kidney disease (CKD). Our previous study demonstrated that endoplasmic reticulum (ER) stress as well as oxidative stress are induced in the hippocampus of CKD mice. The present study evaluated the effects of S-allyl-L-cysteine (SAC) on the hippocampus and kidney dysfunctions of CKD mice. Treatment of the mice with SAC decreased the expression level of 78-kDa glucose-regulated protein (GRP78), an indicator of ER stress, in the hippocampus. SAC also restored the blood urea nitrogen (BUN) level in the blood and the increase in glomerular area in CKD mice. On the other hand, Tempol, a free radical scavenger, did not affect the increase of GRP78 and kidney dysfunction induced by CKD. These results may provide new insight into the therapeutic potency of SAC and its derivatives on cognitive dysfunction in the patients with CKD.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、我が国でもライフスタイルの変化によりCKDや糖尿病などの生活習慣病患者数は増加の一途を辿っている。CKDに伴う合併症の発症は患者の余命および日常生活に大きな影響を与えるため、病態メカニズムの解明や治療法の確立は急務である。小胞体ストレスの関与を解明した本研究の成果は、CKDにおける高次脳機能障害の発症機序の解明にとどまらず、これらの合併症に対する治療薬の開発にも役立つものであると考える。
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] Phlenumdines D and E, new Lycopodium alkaloids from Phlegmariurus nummulariifolius, and their regulatory effects on macrophage differentiation during tumor development2018
Author(s)
Nakayama W, Fujiwara Y, Kosuge Y, Monthakantirat O, Fujikawa K, Watthana S, Kitanaka S, Makino T, Ishiuchia K.
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Journal Title
Phytochemistry Letters
Volume: 29
Pages: 98-103
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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