Pathological role of endoplasmic reticulum stress in the hippocampal dysfunction seen in chronic kidney disease

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08965
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Nihon University
• Principal Investigator: KOSUGE Yasuhiro 日本大学, 薬学部, 准教授 (70383726)
• Co-Investigator(Kenkyū-buntansha): 三枝 禎 日本大学, 松戸歯学部, 教授 (50277456)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 慢性腎臓病 / 海馬 / 記憶 / 尿毒素 / 小胞体ストレス

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.

Free Research Field

神経化学・薬理薬

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。