• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

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

Research Project

Project/Area Number 17K08965
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied pharmacology
Research InstitutionNihon 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
Project Status Completed (Fiscal Year 2019)
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)
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
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.

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。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (26 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (3 results) Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 5 results) Presentation (12 results) (of which Int'l Joint Research: 3 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Salk institute for biological studies(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Salk institute for biological studies(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Salk institute for biological studies(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Neuroprotective mechanisms of S-allyl-L-cysteine in neurological disease.2020

    • Author(s)
      Kosuge Y.
    • Journal Title

      Experimental and Therapeutic Medicine

      Volume: 19(2) Pages: 1565-1569

    • DOI

      10.3892/etm.2019.8391

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bidens pilosa Extract Administered after Symptom Onset Attenuates Glial Activation, Improves Motor Performance, and Prolongs Survival in a Mouse Model of Amyotrophic Lateral Sclerosis2020

    • Author(s)
      Kosuge Yasuhiro、Kaneko Erina、Nango Hiroshi、Miyagishi Hiroko、Ishige Kumiko、Ito Yoshihisa
    • Journal Title

      Oxidative Medicine and Cellular Longevity

      Volume: 2020 Pages: 1-11

    • DOI

      10.1155/2020/1020673

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of Cellular Reactive Oxygen Species by Activation of the EP2 Receptor Contributes to Prostaglandin E2-Induced Cytotoxicity in Motor Neuron-Like NSC-34 Cells2020

    • Author(s)
      Kosuge Yasuhiro、Nango Hiroshi、Kasai Hiroki、Yanagi Takuya、Mawatari Takayuki、Nishiyama Kenta、Miyagishi Hiroko、Ishige Kumiko、Ito Yoshihisa
    • Journal Title

      Oxidative Medicine and Cellular Longevity

      Volume: 2020 Pages: 1-14

    • DOI

      10.1155/2020/6101838

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      Phytochemistry Letters

      Volume: 29 Pages: 98-103

    • DOI

      10.1016/j.phytol.2018.11.010

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Deletion of Bmal1 prevents diet-induced ectopic fat accumulation by controlling oxidative capacity in the skeletal muscle.2018

    • Author(s)
      Wada T, Ichihashi Y, Suzuki E, Kosuge Y, Ishige K, Uchiyama T, Makishima M, Nakao R, Oishi K, Shimba S.
    • Journal Title

      Int J Mol Sci.

      Volume: 19 Issue: 9 Pages: 2813-2813

    • DOI

      10.3390/ijms19092813

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pathophysiological role of prostaglandin E2-induced up-regulation of the EP2 receptor in motor neuron-like NSC-34 cells and lumbar motor neurons in ALS model mice.2018

    • Author(s)
      Kosuge Y, Miyagishi H, Yoneoka Y, Yoneda K, Nango H, Ishige K, Ito Y.
    • Journal Title

      Neurochem Int.

      Volume: 印刷中 Pages: 132-139

    • DOI

      10.1016/j.neuint.2017.06.013

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Relevance of the hippocampal endoplasmic reticulum stress response in a mouse model of chronic kidney disease.2018

    • Author(s)
      Kosuge Y, Osada N, Shimomura A, Miyagishi H, Wada T, Ishige K, Shimba S, Ito Y.
    • Journal Title

      Neurosci Lett.

      Volume: 677 Pages: 26-31

    • DOI

      10.1016/j.neulet.2018.04.021

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Indirubin derivatives protect against endoplasmic reticulum stress-induced cytotoxicity and down-regulate CHOP levels in HT22 cells.2017

    • Author(s)
      Kosuge Y, Saito H, Haraguchi T, Ichimaru Y, Ohashi S, Miyagishi H, Kobayashi S, Ishige K, Miyairi S, Ito Y.
    • Journal Title

      Bioorg Med Chem Lett.

      Volume: 27 Issue: 23 Pages: 5122-5125

    • DOI

      10.1016/j.bmcl.2017.10.069

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prostaglandin E2 facilitates neurite outgrowth in a motor neuron-like cell line, NSC-342017

    • Author(s)
      Nango, Hiroshi; Kosuge, Yasuhiro; Miyagishi, Hiroko; Sugawa, Kosuke; Ito, Yoshihisa; Ishige, Kumiko
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 135 Issue: 2 Pages: 64-71

    • DOI

      10.1016/j.jphs.2017.09.001

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 宮古ビデンス・ピローサは、筋萎縮性側索硬化症マウスの運動ニューロン死を抑制し、運動機能を改善し、生存期間を延長する.2020

    • Author(s)
      小菅 康弘, 南郷 拓嗣, 設樂 尊人, 塩原 頼太, 宮岸 寛子, 石毛 久美子, 伊藤 芳久.
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Methylphenidateの小胞体ストレス誘発細胞死に対する保護効果.2020

    • Author(s)
      馬場 清香, 小菅 康弘, 三浦 基文, 樫原 利佳, 南郷 拓嗣, 宮岸 寛子, 鳥山 正晴, 本橋 重康, 石毛 久美子.
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] MOLECULAR MECHANISM FOR THE NEUROPROTECTIVE EFFECT OF S-ALLYL-L-CYSTEINE AGAINST ENDOPLASMIC RETICULUM STRESS-INDUCED NEURONAL DEATH.2019

    • Author(s)
      Yasuhiro Kosuge, Toru Imai, Hiroshi Nango, Hiroko Miyagishi, Yoshihisa Ito, Kumiko Ishige.
    • Organizer
      2019 International Garlic Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 成熟ニンニク由来成分S-allyl-L-cysteineは慢性腎臓病モデルマウスにおける海馬のストレス増加を抑制する2019

    • Author(s)
      小菅 康弘, 宮岸 寛子, 八木 沙英子, 高橋 裕也, 下村 晃子, 南郷 拓嗣, 石毛 久美子, 伊藤 芳久.
    • Organizer
      第21回応用薬理シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 注意欠陥・多動性障害(ADHD)治療薬の小胞体ストレス誘発細胞死に対する保護効果.2019

    • Author(s)
      樫原 利佳, 小菅 康弘, 堀越 苑子, 南郷 拓嗣, 宮岸 寛子, 石毛 久美子.
    • Organizer
      生体機能と創薬シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] Prostaglandin D2の運動ニューロン様株化細胞NSC-34の神経突起伸長に及ぼす影響.2019

    • Author(s)
      吉村 奈菜, 小菅 康弘, 南郷 拓嗣, 宮岸 寛子, 石毛 久美子.
    • Organizer
      生体機能と創薬シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 慢性腎臓病モデルマウスにおける海馬小胞体ストレス応答に対するS-allyl-L-cysteineの保護効果2018

    • Author(s)
      小菅康弘、八木沙英子、大山みどり、高橋裕也、下村晃子、長田暢弘、南郷拓嗣、石毛久美子、伊藤芳久
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 低用量ストレプトゾトシン誘発緩徐進行性糖尿病モデルマウス海馬における細胞内シグナル伝達系の変化2018

    • Author(s)
      大山みどり、小菅康弘、八木沙英子、南郷拓嗣、石毛久美子、伊藤芳久
    • Organizer
      第62回日本薬学会関東支部大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 5/6腎摘慢性腎不全モデルマウスの海馬における小胞体ストレス関連因子の発現変化2018

    • Author(s)
      八木沙英子、小菅康弘、大山みどり、下村晃子、長田暢弘、石毛久美子、伊藤芳久
    • Organizer
      第62回日本薬学会関東支部大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Pathogenic role of EP2 receptors up-regulation in motor neuron-like NSC-34 cells and lumbar motor neurons in ALS model mice2018

    • Author(s)
      Kosuge Y, Nango H, Ishige K, Ito Y.
    • Organizer
      The 18th World Congress ofBasic and Clinical Pharmacology (WCP2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Prostaglandin E2 induces differentiation of NSC-34 cells with neuron-like features2018

    • Author(s)
      Nango H, Kosuge Y, Sato M, Shibikawa Y, Tazaki M, Ito Y, Ishige K.
    • Organizer
      The 18th World Congress ofBasic and Clinical Pharmacology (WCP2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] インディルビン誘導体の小胞体ストレス誘発細胞死に対する保護効果2018

    • Author(s)
      小菅 康弘, 齋藤 弘明, 南郷 拓嗣, 石毛 久美子, 宮入 伸一, 伊藤 芳久
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Remarks] 宮古ビデンス・ピローサRエキス末がALSモデルマウスの病態を改善、延命効果を示すことを発見

    • URL

      https://www.pha.nihon-u.ac.jp/news/20200204/

    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 薬物送達用組成物および医薬組成物2019

    • Inventor(s)
      金沢貴憲、小菅康弘
    • Industrial Property Rights Holder
      学校法人日本大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-115688
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi