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Role of the ER stress-related molecule ATF6b in a mouse model of multiple sclerosis

Research Project

Project/Area Number 18K06500
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46020:Anatomy and histopathology of nervous system-related
Research InstitutionKanazawa University

Principal Investigator

Hori Osamu  金沢大学, 医学系, 教授 (60303947)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords小胞体ストレス / 脱髄 / 神経炎症 / 神経細胞 / グリア細胞 / 脱髄疾患 / 神経変性 / 炎症応答
Outline of Final Research Achievements

It has been reported that endoplasmic reticulum (ER) stress is involved in the pathology of multiple sclerosis and its experimental animal model, EAE. We, therefore, studied the expression and the possible role of ATF6b, an ER stress-related gene, in a mouse EAE model. When EAE was introduced to WT mice, ATF6b was upregulated in both neurons and oligodendrocytes in the spinal cord. Furthermore, when similar experiments were performed with AFT6b KO mice, the paralysis and demyelination was severer than those in WT mice. These results suggest that ATF6b protects neurons and oligodendrocytes in the pathology of EAE.

Academic Significance and Societal Importance of the Research Achievements

多発性硬化症は原因不明の中枢性炎症性脱髄疾患である。今回の研究から、小胞体ストレスに関係するATF6bという分子がその病態を制御していることが明らかになった。今後、ATF6bの機能を促進したり、量を増加させたりすることで脱髄が抑制できるのではないかと期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (41 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (19 results) (of which Int'l Joint Research: 17 results,  Peer Reviewed: 19 results,  Open Access: 15 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results) Remarks (4 results) Patent(Industrial Property Rights) (1 results) Funded Workshop (1 results)

  • [Int'l Joint Research] ニューヨーク大学(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] ニューヨーク大学(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Abnormal social behavior and altered gene expression in mice lacking NDRG22021

    • Author(s)
      Takarada-Iemata Mika、Yoshihara Toru、Okitani Nahoko、Iwata Keiko、Hattori Tsuyoshi、Ishii Hiroshi、Roboon Jureepon、Nguyen Dinh Thi、Fan Qiyan、Tamatani Takashi、Nishiuchi Takumi、Asano Masahide、Hori Osamu
    • Journal Title

      Neuroscience Letters

      Volume: 743 Pages: 135563-135563

    • DOI

      10.1016/j.neulet.2020.135563

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pyramid-Shape Crossings and Intercrossing Fibers Are Key Elements for Construction of the Neural Network in the Superficial White Matter of the Human Cerebrum2020

    • Author(s)
      Shinohara Harumichi、Liu Xiaoliang、Nakajima Riho、Kinoshita Masashi、Ozaki Noriyuki、Hori Osamu、Nakada Mitsutoshi
    • Journal Title

      Cerebral Cortex

      Volume: - Issue: 10 Pages: 5218-5228

    • DOI

      10.1093/cercor/bhaa080

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Direct evidence of the relationship between brain metastatic adenocarcinoma and white matter fibers: A fiber dissection and diffusion tensor imaging tractography study2020

    • Author(s)
      Liu Xiaoliang、Kinoshita Masashi、Shinohara Harumichi、Hori Osamu、Ozaki Noriyuki、Hatta Toshihisa、Honma Satoru、Nakada Mitsutoshi
    • Journal Title

      Journal of Clinical Neuroscience

      Volume: S0967-5852 Pages: 55-61

    • DOI

      10.1016/j.jocn.2020.05.043

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neuroprotective effects of endogenous secretory receptor for advanced glycation end-products in brain ischemia2020

    • Author(s)
      Simizu Y, Harashima A, Munesue S, Oishi M, Hattori T, Hori O, Kitao Y, Yamamoto H, Leerach N, Nakada M, Yamamoto Y, Hayashi Y
    • Journal Title

      Aging Dis

      Volume: 11 Issue: 3 Pages: 547-547

    • DOI

      10.14336/ad.2019.0715

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Deletion of CD38 and supplementation of NAD + attenuate axon degeneration in a mouse facial nerve axotomy model2020

    • Author(s)
      Takaso Y, Noda M, Hattori T, Roboon J, Hatano M, Sugimoto H, Brenner C, Yamamoto Y, Okamoto H, Higashida H, Ito M, Yoshizaki T, Hori O.
    • Journal Title

      Sci Rep

      Volume: 10 Issue: 1 Pages: 17795-17795

    • DOI

      10.1038/s41598-020-73984-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Therapeutics potentiating microglial p21-Nrf2 axis can rescue neurodegeneration caused by neuroinflammation2020

    • Author(s)
      A. Nakano-Kobayashi1,*, A. Fukumoto2, A. Morizane2, D. T. Nguyen3, T. M. Le3, K. Hashida3, T. Hosoya4, R. Takahashi5,J. Takahashi2, O. Hori3 and M. Hagiwara1
    • Journal Title

      Science Advances

      Volume: 6 Issue: 46 Pages: 1-12

    • DOI

      10.1126/sciadv.abc1428

    • NAID

      120006898186

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Does the superior fronto-occipital fascicle exist in the human brain? Fiber dissection and brain functional mapping in 90 patients with gliomas2020

    • Author(s)
      Liu Xiaoliang、Kinoshita Masashi、Shinohara Harumichi、Hori Osamu、Ozaki Noriyuki、Nakada Mitsutoshi
    • Journal Title

      NeuroImage: Clinical

      Volume: 25 Pages: 102192-102192

    • DOI

      10.1016/j.nicl.2020.102192

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CD38, CD157, and RAGE as Molecular Determinants for Social Behavior.2019

    • Author(s)
      .Higashida H, Hashii M, Tanaka Y, Matsukawa S, Higuchi Y, Gabata R, Tsubomoto M, Seishima N, Teramachi M, Kamijima T, Hattori T, Hori O, Tsuji C, Cherepanov SM, Shabalova AA, Gerasimenko M, Minami K, Yokoyama S, Munesue SI, Harashima A, Yamamoto Y, Salmina AB, Lopatina O.
    • Journal Title

      Cells.

      Volume: 9(1) Issue: 1 Pages: 62-62

    • DOI

      10.3390/cells9010062

    • NAID

      120006859506

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neuroprotective Effects of Endogenous Secretory Receptor for Advanced Glycation End-products in Brain Ischemia2019

    • Author(s)
      Yu Shimizu, Ai Harashima, Seiichi Munesue, Masahiro Oishi, Tsuyoshi Hattori, Osamu Hori, Yasuko Kitao, Hiroshi Yamamoto, Nontaphat Leerach, Mitsutoshi Nakada, Yasuhiko Yamamoto, Yasuhiko Hayashi
    • Journal Title

      Aging and Disease

      Volume: 印刷中

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Soluble receptor for advanced glycation end products as a biomarker of symptomatic vasospasm in subarachnoid hemorrhage.2019

    • Author(s)
      Aida Y, Kamide T, Ishii H, Kitao Y, Uchiyama N, Nakada M, Hori O.
    • Journal Title

      J Neurosurg.

      Volume: Nov 1 Issue: 1 Pages: 1-9

    • DOI

      10.3171/2019.8.jns191269

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Deletion of CD38 Suppresses Glial Activation and Neuroinflammation in a Mouse Model of Demyelination2019

    • Author(s)
      Roboon Jureepon、Hattori Tsuyoshi、Ishii Hiroshi、Takarada-Iemata Mika、Le Thuong Manh、Shiraishi Yoshitake、Ozaki Noriyuki、Yamamoto Yasuhiko、Sugawara Akira、Okamoto Hiroshi、Higashida Haruhiro、Kitao Yasuko、Hori Osamu
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 13 Pages: 258-258

    • DOI

      10.3389/fncel.2019.00258

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Caspase-1 initiates apoptosis in the absence of gasdermin D2019

    • Author(s)
      Tsuchiya K, Nakajima S, SHosojima S, Nguyen DT, Hattori T, Le TM, Hori O, Mahib MR, Yamaguchi Y, Miura M, Kinoshita T, Kushiyama H, Sakurai M, Shiroishi T, Suda T
    • Journal Title

      Nature Communications

      Volume: In press Issue: 1 Pages: 2091-2091

    • DOI

      10.1038/s41467-019-09753-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Caspase-1 initiates apoptosis in the absence of gasdermin D2019

    • Author(s)
      Tsuchiya K Nakajima S, Hosojima S, Nguyen DT, Hattori T, Le TM, Hori O, Mahib MR, Yamaguchi Y, Miura M, Kinoshita T, Kushiyama H, Sakurai M, Shiroishi T, Suda T
    • Journal Title

      Nat Commun

      Volume: 印刷中

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pre-administration of low-dose methamphetamine enhances movement and neural activity after high-dose methamphetamine administration in the striatum2019

    • Author(s)
      Takeichi T, Hori O, Hattori T, Kiryu K, Zuka M, Kitamura O
    • Journal Title

      Neurosci Lett

      Volume: 703 Pages: 119-124

    • DOI

      10.1016/j.neulet.2019.03.023

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microglial activation in the cochlear nucleus after early hearing loss in rats.2019

    • Author(s)
      Noda M, Hatano M, Hattori T, Takarada-Iemata M, Shinozaki T, Sugimoto H, Ito M, Yoshizaki T, Hori O.
    • Journal Title

      Auris Nasus Larynx.

      Volume: 印刷中 Issue: 5 Pages: 716-723

    • DOI

      10.1016/j.anl.2019.02.006

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice.2019

    • Author(s)
      Yamamoto Y, Liang M, Munesue S, Deguchi K, Harashima A, Furuhara K, Yuhi T, Zhong J, Akther S, Goto H, Eguchi Y, Kitao Y, Hori O, Shiraishi Y, Ozaki N, Shimizu Y, Kamide T, Yoshikawa A, Hayashi Y, Nakada M, Lopatina O, Gerasimenko M, Komleva Y, Malinovskaya N, Salmina AB, Asano M, Nishimori K, Higashida H et al.,
    • Journal Title

      Commun Biol

      Volume: 2 Issue: 1 Pages: 76-76

    • DOI

      10.1038/s42003-019-0325-6

    • NAID

      120006605138

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inhibition of nuclear factor-κB p65 phosphorylation by 3,4-dihydroxybenzalacetone and caffeic acid phenethyl ester.2018

    • Author(s)
      Takakura K, Takatou S, Tomiyama R, Le TM, Nguyen DT, Nakamura Y, Konishi T, Matsugo S, Hori O.
    • Journal Title

      J Pharmacol Sci

      Volume: 137(3) Issue: 3 Pages: 248-255

    • DOI

      10.1016/j.jphs.2018.07.003

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] N-myc downstream-regulated gene 2 protects blood-brain barrier integrity following cerebral ischemia2018

    • Author(s)
      Takarada-Iemata Mika、Yoshikawa Akifumi、Ta Hieu Minh、Okitani Nahoko、Nishiuchi Takumi、Aida Yasuhiro、Kamide Tomoya、Hattori Tsuyoshi、Ishii Hiroshi、Tamatani Takashi、Le Thuong Manh、Roboon Jureepon、Kitao Yasuko、Matsuyama Tomohiro、Nakada Mitsutoshi、Hori Osamu
    • Journal Title

      Glia

      Volume: 印刷中 Issue: 7 Pages: 1432-1446

    • DOI

      10.1002/glia.23315

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Ndrg2 deficiency ameliorates neurodegeneration in experimental autoimmune encephalomyelitis2018

    • Author(s)
      Le Thuong Manh、Takarada-Iemata Mika、Ta Hieu Minh、Roboon Jureepon、Ishii Hiroshi、Tamatani Takashi、Kitao Yasuko、Hattori Tsuyoshi、Hori Osamu
    • Journal Title

      Journal of neurochemistry

      Volume: 印刷中 Issue: 2 Pages: 139-153

    • DOI

      10.1111/jnc.14294

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] アストロサイトCD38による社会性記憶の制2021

    • Author(s)
      服部 剛志、堀 修
    • Organizer
      第126回日本解剖学会総会・全国学術集会・第98回日本生理学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 脳損傷後の小胞体ストレス応答の細胞・時間2021

    • Author(s)
      範 啓エン、宝田 美佳、堀 修
    • Organizer
      第126回日本解剖学会総会・全国学術集会・第98回日本生理学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] マウス下垂体血管内皮細胞におけるCD38の発現2021

    • Author(s)
      坂賀 綾、堀 修
    • Organizer
      第126回日本解剖学会総会・全国学術集会・第98回日本生理学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Neuroprotective role of glial ATF6α pathway in optic nerve injury2019

    • Author(s)
      宝田美佳、堀修
    • Organizer
      第42回日本神経科学大会・第62回日本神経化学会合同年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 脳発達と社会性行動におけるアストロサイトCD38の役割2019

    • Author(s)
      服部剛志、堀修
    • Organizer
      第49回日本神経精神薬理学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] DAMPs-dependent neutrophil migration is critical pathology in cerebral vasospasm after SAH2019

    • Author(s)
      石井宏史、堀修
    • Organizer
      第62回日本脳循環代謝学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 脳梗塞後のグリアストレス応答を介した神経血管保護作用2019

    • Author(s)
      第42回日本分子生物学会
    • Organizer
      第42回日本分子生物学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 脳虚血病態におけるストレス応答性分子の保護的効果2018

    • Author(s)
      宝田美佳、堀修
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Protective role of NDRG2 in blood-brain barrier integrity following ischemia2018

    • Author(s)
      宝田美佳、堀修
    • Organizer
      International Conference on Neurovascular and Neurodegenerative Diseases
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] アストロサイトCD38による神経発達制御機構2018

    • Author(s)
      服部剛志、堀修
    • Organizer
      日本解剖学会 第78回中部支部学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Peripheral leukocyte accumulation in the brain is critical pathology of cerebral vasospasm/neuronal dysfunction after subdural arachnoid hemorrhage2018

    • Author(s)
      石井宏史、堀修
    • Organizer
      日本解剖学会 第78回中部支部学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 視神経傷害後の網膜神経節細胞生存における小胞体ストレス応答ATF6経路の役割2018

    • Author(s)
      宝田美佳、堀修
    • Organizer
      日本解剖学会 第78回中部支部学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] The role of CD38 for neuronal and glial development2018

    • Author(s)
      服部剛志、堀修
    • Organizer
      第61回日本神経化学会
    • Related Report
      2018 Research-status Report
  • [Presentation] アストロサイトによる脳梗塞後の血液脳関門制御2018

    • Author(s)
      宝田美佳、堀修
    • Organizer
      第61回日本神経化学会
    • Related Report
      2018 Research-status Report
  • [Remarks] 金沢大学医薬保険研究域医学系 神経解剖学

    • Related Report
      2020 Annual Research Report
  • [Remarks]

    • URL

      https://med03.w3.kanazawa-u.ac.jp/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 金沢大学医薬保健研究域医学系 神経解剖学

    • URL

      http://med03.w3.kanazawa-u.ac.jp/

    • Related Report
      2019 Research-status Report
  • [Remarks]

    • URL

      http://med03.w3.kanazawa-u.ac.jp/

    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] 脳血管攣縮抑制剤2020

    • Inventor(s)
      石井 宏史、堀 修
    • Industrial Property Rights Holder
      石井 宏史、堀 修
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-152739
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Funded Workshop] New Frontier in Neuroscience 20202020

    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2024-12-25  

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