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Development of Regenerative Therapy of Osmotic Demyelination Syndrome

Research Project

Project/Area Number 19K17724
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53040:Nephrology-related
Research InstitutionFujita Health University

Principal Investigator

Fujisawa Haruki  藤田医科大学, 医学部, 講師 (50836830)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords浸透圧性脱髄 / 低ナトリウム血症 / 再生治療 / オリゴデンドロサイト / 電解質 / 再生
Outline of Research at the Start

浸透圧性脱髄は、低ナトリウム(Na)血症治療時の合併症で、血清Na濃度が急速に上昇することによって発症し、意識障害、四肢麻痺、偽性球麻痺、呼吸障害等の一部は不可逆的な症状を呈し、しばしば致死的になる重篤な疾患である。申請者のグループではその予防法について研究を続けてきたが、完全に発症を防止することはできず、一旦発症した場合にはその治療法は存在しない。そこで、本研究では動物モデルを用いて髄鞘再生の促進による浸透圧性脱髄の治療法を開発することを目的とした。本研究により、浸透圧性脱髄、さらにはその他の脱髄疾患の治療への臨床応用が期待される。

Outline of Final Research Achievements

Osmotic demyelination syndrome (ODS) is a complication during treatment of chronic hyponatremia. It develops as a result of a rapid increase in serum Na concentrations and is associated with neurologic morbidity and mortality. Once the disease develops, there is no treatment for it. Therefore, the purpose of this study is to develop a treatment for ODS by promoting remyelination using an animal model. As a preliminary step for developing ODS model mice, we succeeded in producing a mouse model of chronic hyponatremia. Using this mouse model, we conducted behavioral analysis and found that chronic hyponatremia causes memory impairment and enhanced anxiety-like behavior. We are now elucidating the mechanism of chronic hyponatremia-induced anxiety and developing treatment for it.

Academic Significance and Societal Importance of the Research Achievements

本研究で、浸透圧性脱髄の前段階である慢性低Na血症モデルマウスの作製に成功し、論文発表を行った。これを用いて、慢性低Na血症が神経症状を生じることを明らかにした。今後、このマウスを用いて慢性低Na血症による神経症状のメカニズムの解明を計画している。さらに、これを基にした治療法の開発も予定しており、これにより慢性低Na血症患者のquality of lifeの向上に寄与すると考えられる。また、学術的にも、いまだ全貌が明らかになっていない、神経組織の浸透圧受容のメカニズム、細胞体積調節のメカニズムおよびそれによる神経機能の変化のメカニズムの解明につながるものと考えられる。

Report

(4 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (20 results)

All 2022 2021 2020 2019

All Journal Article (14 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 4 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Ketoacidosis, Hypertriglyceridemia and Acute Pancreatitis Induced by Soft Drink Polydipsia in a Patient with Occult Central Diabetes Insipidus2022

    • Author(s)
      Tsujimoto Yasutaka、Nakamura Tomoaki、Onishi Jun、Ishimaru Naoto、Iwata Naoko、Fujisawa Haruki、Suzuki Atsushi、Sugimura Yoshihisa、Chihara Kazuo
    • Journal Title

      Internal Medicine

      Volume: 61 Issue: 3 Pages: 365-371

    • DOI

      10.2169/internalmedicine.7663-21

    • NAID

      130008150317

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2022-02-01
    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lymphocytic panhypophysitis and anti-rabphilin-3A antibody with pulmonary sarcoidosis2022

    • Author(s)
      Takahashi Yuka、Kameda Hiraku、Miya Aika、Nomoto Hiroshi、Cho Kyu Yong、Nakamura Akinobu、Nishimura Hiroki、Kimura Hirokazu、Suzuki Masaru、Konno Satoshi、Shimizu Ai、Matsuno Yoshihiro、Okamoto Michinari、Motegi Hiroaki、Iwata Naoko、Fujisawa Haruki、Suzuki Atsushi、Sugimura Yoshihisa、Miyoshi Hideaki、Atsumi Tatsuya
    • Journal Title

      Pituitary

      Volume: 25 Issue: 2 Pages: 321-327

    • DOI

      10.1007/s11102-021-01200-0

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A 7-year-old boy with central diabetes insipidus presenting with thickened pituitary stalk and anti-rabphilin-3A antibody positivity2022

    • Author(s)
      Morota Kazutaka、Tadokoro Hiroaki、Sawano Kentaro、Watanabe Kenichi、Iwata Naoko、Fujisawa Haruki、Suzuki Atsushi、Sugimura Yoshihisa、Nagasaki Keisuke
    • Journal Title

      Journal of Pediatric Endocrinology and Metabolism

      Volume: 0 Issue: 5 Pages: 687-690

    • DOI

      10.1515/jpem-2021-0674

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] High Protein Diet Feeding Aggravates Hyperaminoacidemia in Mice Deficient in Proglucagon-Derived Peptides2022

    • Author(s)
      Ueno Shinji、Seino Yusuke、Hidaka Shihomi、Maekawa Ryuya、Takano Yuko、Yamamoto Michiyo、Hori Mika、Yokota Kana、Masuda Atsushi、Himeno Tatsuhito、Tsunekawa Shin、Kamiya Hideki、Nakamura Jiro、Kuwata H、Fujisawa H、Shibata M、Takayanagi T、Sugimura Y、Yabe Daisuke、Hayashi Yoshitaka、Suzuki Atsushi
    • Journal Title

      Nutrients

      Volume: 14 Issue: 5 Pages: 975-975

    • DOI

      10.3390/nu14050975

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Studies on anti-rabphilin-3A antibodies in 15 consecutive patients presenting with central diabetes insipidus at a single referral center2022

    • Author(s)
      Arihara Zenei、Sakurai Kanako、Niitsuma Satsuki、Sato Ryota、Yamada Shozo、Inoshita Naoko、Iwata Naoko、Fujisawa Haruki、Watanabe Takashi、Suzuki Atsushi、Takahashi Kazuhiro、Sugimura Yoshihisa
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1

    • DOI

      10.1038/s41598-022-08552-y

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Older adults with a higher frailty index tend to have electrolyte imbalances2022

    • Author(s)
      Fujisawa Chisato、Umegaki Hiroyuki、Sugimoto Taiki、Huang Chi Hsien、Fujisawa Haruki、Sugimura Yoshihisa、Kuzuya Masafumi、Toba Kenji、Sakurai Takashi
    • Journal Title

      Experimental Gerontology

      Volume: 163 Pages: 111778-111778

    • DOI

      10.1016/j.exger.2022.111778

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mild hyponatremia is associated with low skeletal muscle mass, physical function impairment, and depressive mood in the elderly2021

    • Author(s)
      Fujisawa Chisato、Umegaki Hiroyuki、Sugimoto Taiki、Samizo Satoshi、Huang Chi Hsien、Fujisawa Haruki、Sugimura Yoshihisa、Kuzuya Masafumi、Toba Kenji、Sakurai Takashi
    • Journal Title

      BMC Geriatrics

      Volume: 21 Issue: 1 Pages: 15-15

    • DOI

      10.1186/s12877-020-01955-4

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of isolated hypothalamitis with a literature review and a comparison with autoimmune hypophysitis2021

    • Author(s)
      Niri Tetsuro、Horie Ichiro、Kawahara Hiromi、Ando Takao、Fukuhara Noriaki、Nishioka Hiroshi、Inoshita Naoko、Fujisawa Haruki、Suzuki Atsushi、Sugimura Yoshihisa、Abiru Norio、Kawakami Atsushi
    • Journal Title

      Endocrine Journal

      Volume: 68 Issue: 1 Pages: 119-127

    • DOI

      10.1507/endocrj.EJ20-0300

    • NAID

      130007975896

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vasopressin escape and memory impairment in a model of chronic syndrome of inappropriate secretion of antidiuretic hormone in mice2021

    • Author(s)
      Kawakami Tsukasa、Fujisawa Haruki、Nakayama Shogo、Yoshino Yasumasa、Hattori Satoko、Seino Yusuke、Takayanagi Takeshi、Miyakawa Tsuyoshi、Suzuki Atsushi、Sugimura Yoshihisa
    • Journal Title

      Endocrine Journal

      Volume: 68 Issue: 1 Pages: 31-43

    • DOI

      10.1507/endocrj.EJ20-0289

    • NAID

      130007975882

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] II. Hypernatremia and Endocrine Disorders2020

    • Author(s)
      Fujisawa Haruki、Sugimura Yoshihisa
    • Journal Title

      Nihon Naika Gakkai Zasshi

      Volume: 109 Issue: 4 Pages: 712-717

    • DOI

      10.2169/naika.109.712

    • NAID

      130008023559

    • Related Report
      2020 Research-status Report
  • [Journal Article] 尿崩症診断におけるcopeptinの意義2020

    • Author(s)
      藤沢治樹, 椙村益久
    • Journal Title

      月刊糖尿病・内分泌代謝科

      Volume: 51 Pages: 473-476

    • NAID

      40022439007

    • Related Report
      2020 Research-status Report
  • [Journal Article] 【内分泌疾患に関連する緊急症への対応-最近の進歩】低ナトリウム血症2020

    • Author(s)
      藤沢治樹, 椙村益久
    • Journal Title

      月刊糖尿病・内分泌代謝科

      Volume: 50 Pages: 266-269

    • Related Report
      2020 Research-status Report
  • [Journal Article] 薬剤性低ナトリウム血症2019

    • Author(s)
      藤沢治樹、椙村益久
    • Journal Title

      内分泌・糖尿病・代謝内科

      Volume: 49 Pages: 125-128

    • Related Report
      2019 Research-status Report
  • [Journal Article] リンパ球性漏斗下垂体後葉炎の6歳児例2019

    • Author(s)
      西本由佳, 前田明彦, 椙村益久, 藤沢治樹, 鈴木敦詞, 萩野紘平, 丸金拓蔵, 澤井孝典, 島田誠一, 白石泰資, 荒木まり子
    • Journal Title

      小児リウマチ

      Volume: 10 Pages: 33-37

    • NAID

      130008000982

    • Related Report
      2019 Research-status Report
  • [Presentation] 慢性の抗利尿ホルモン不適切分泌症候群(SIADH) マウスモデルにおけるバソプレシンエスケープと 記憶障害2022

    • Author(s)
      藤沢 治樹、中山 将吾、川上 司、上野 慎士、淺田 陽平、 戸松 瑛介、吉野 寧維、平塚 いづみ、清野 祐介、四馬田 恵、 高柳 武志、椙村 益久、鈴木 敦詞
    • Organizer
      第94回日本内分泌学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 中枢性尿崩症の原因と抗rabphilin-3A抗体2020

    • Author(s)
      在原善英、桜井華奈子、新妻さつき、佐藤良太、山田正三、井下尚子、藤沢治樹、鈴木敦詞、椙村益久
    • Organizer
      第93回日本内分泌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] SIADH慢性低ナトリウム(Na)血症モデルマウスの作製2020

    • Author(s)
      川上 司, 藤沢 治樹, 中山 将吾, 淺田 陽平, 増田 富, 戸松 瑛介, 吉野 寧維, 平塚 いづみ, 清野 祐介, 四馬田 恵, 高柳 武志, 椙村 益久, 鈴木 敦詞
    • Organizer
      第93回日本内分泌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Chronic Hyponatremia Causes Neurologic and Psychologic Impairments2020

    • Author(s)
      Haruki Fujisawa, Hiroyuki Mizoguchi, Hideyuki Takeuchi, Yukio Komatsu, Atsushi Suzuki, Yoshihisa Sugimura
    • Organizer
      第10回武田科学振興財団薬科学シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] リンパ球性漏斗下垂体後葉炎(LINH)診断マーカーとしての抗Rabphilin-3A抗体の有用性の検討2019

    • Author(s)
      藤沢 治樹, 椙村 益久, 中山 将吾, 川上 司, 淺田 陽平, 増田 富, 戸松 瑛介, 吉野 寧維, 平塚 いづみ, 清野 祐介, 四馬田 恵, 高柳 武志, 鈴木 敦詞
    • Organizer
      第92回日本内分泌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] NMDA receptor antagonist prevents cell death in the hippocampal dentate gyrus induced by hyponatremia accompanying adrenal insufficiency in rats2019

    • Author(s)
      H. FUJISAWA, H. IZUMIDA, A. SUZUKI, Y. SUGIMURA
    • Organizer
      Neuroscience 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2024-01-30  

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