Molecular mechanisms of pathological modification by altered psychiatric states
| Project/Area Number |
21K19364
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2021-07-09 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | ゲートウェイ反射 / IL-6アンプ / ストレス / 自己反応性T細胞 / 関節リウマチ / 中枢神経ループス / ケモジェネティクス |
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| Outline of Research at the Start |
精神、心理状態の変化が身体に影響を及ぼすことは経験的にも知られているが、その分子機構は解明されておらず、それを客観的に評価できるバイオマーカーは存在しない。さらに、好ましくない環境や逆に楽しい環境などさまざまな心理状態が脳内でどのような神経回路を形成し健康や病気に影響するのかもほとんど理解されていない。これらの解明は現象が複雑であるがゆえ非常に挑戦的な研究課題であるが、G反射という申請者の独自の発見である観点に絞ってアプローチすることで精神、心理状態の変容と病気の関係を捉えられる可能性は高い。また、病気に関連する精神、心理状態の変容のヒトバイオマーカーが開発されれば、病気、病態の予防に繋がる。
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| Outline of Final Research Achievements |
With stress gateway (SG) reflex pathology model, we identified five membrane and soluble molecules induced in a stress-dependent manner, and succeeded in almost completely suppressing stress-dependent pathology by intracerebral administration of specific antibodies (US 17/271300, JP application 2020-539659, EP19855524.5 patent pending). For one molecule, we have already established monoclonal antibodies, which can suppress the pathology, paving the way for future clinical applications. In addition to the reproduction of SG reflex using chemogenetics, we also newly discovered “remote inflammation G-reflex”, which could explain the mechanism of symmetric inflammation of rheumatoid arthritis, and clarified the molecular mechanism of neuropsychiatric systemic lupus erythematosus induced by stress.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究を通して、ストレス依存性病態の分子機構の一端の解明や、病態制御に関与する分子群を同定することに成功した。今後、これら分子の病態形成機能を明らかにしつつ、ストレス依存的に末梢血中で産生が増強される分子群を同定することで、疾患を早期に診断・治療できる新規のストレスマーカーや治療標的の開発が期待できる。
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Report
(3 results)
Research Products
(90 results)
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[Journal Article] Dupuytren's contracture-associated SNPs increase SFRP4 expression in nonimmune cells including fibroblasts to enhance inflammation development2023
Author(s)
Kida H, Jiang JJ, Matsui Y, Takahashi I, Hasebe R, Kawamura D, Endo T, Shibayama H, Kondoh M, Nishio Y, Nishida K, Matsuno Y, Oikawa T, Kubota S, Hojyo S, Iwasaki N, Hashimoto S, Tanaka Y, Murakami M.
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Journal Title
Int Immunol.
Volume: dxad004
Issue: 7
Pages: 303-312
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Antibody feedback contributes to facilitating the development of Omicron-reactive memory B cells in SARS-CoV-2 mRNA vaccinees2023
Author(s)
Inoue T, Shinnakasu R, Kawai C, Yamamoto H, Sakakibara S, Ono C, Itoh Y, Terooatea T, Yamashita K, Okamoto T, Hashii N, Ishii-Watabe A, Butler NS, Matsuura Y, Matsumoto H, Otsuka S, Hiraoka K, Teshima T, Murakami M, Kurosaki T.
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Journal Title
J Exp Med.
Volume: 220(2)
Issue: 2
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Zoobiquity experiments show the importance of the local MMP9-plasminogen axis in inflammatory bowel diseases in both dogs and patients.2023
Author(s)
Takeshi Yamasaki, Noriyuki Nagata, Toru Atsumi, Rie Hasebe, Yuki Tanaka, Izuru Ohki, Shimpei Kubota, Yuta Shinohara, Yong Bin Teoh, Nozomu Yokoyama, Noboru Sasaki, Kensuke Nakamura, Hiroshi Ohta, Takehiko Katsurada, Yoshihiro Matsuno, Shintaro Hojyo, Shigeru Hashimoto, Mitsuyoshi Takiguchi, Masaaki Murakami.
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Journal Title
International immunology
Volume: -
Issue: 7
Pages: 313-326
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] SARS-CoV-2 Omicron detection by antigen tests using saliva2022
Author(s)
Murakami K, Iwasaki S, Oguri S, Tanaka K, Suzuki R, Hayasaka K, Fujisawa S, Watanabe C, Konno S, Yokota I, Fukuhara T, Murakami M, Teshima T.
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Journal Title
J Clin Virol Plus.
Volume: 2(4)
Issue: 4
Pages: 100109-100109
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Sjogren's syndrome-associated SNPs increase GTF2I expression in salivary gland cells to enhance inflammation development.2021
Author(s)
Shimoyama S, Nakagawa I, Jiang JJ, Matsumoto I, Chiorini JA, Hasegawa Y, Ohara O, Hasebe R, Ota M, Uchida M, Kamimura D, Hojyo S, Tanaka Y, Atsumi T, Murakami M.
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Journal Title
Int Immunol.
Volume: 33
Issue: 8
Pages: 423-434
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Rhodobacter azotoformans LPS (RAP99-LPS) Is a TLR4 Agonist That Inhibits Lung Metastasis and Enhances TLR3-Mediated Chemokine Expression.2021
Author(s)
Murakami K, Kamimura D, Hasebe R, Uchida M, Abe N, Yamamoto R, Jiang JJ, Hidaka Y, Nakanishi Y, Fujita S, Toda Y, Toda N, Tanaka H, Akira S, Tanaka Y, Murakami M.
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Journal Title
Front Immunol.
Volume: 12
Pages: 675909-675909
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Glycogen synthase kinase 3β/CCR6-positive bone marrow cells correlate with disease activity in multicentric Castleman disease-TAFRO2021
Author(s)
Abe N, Kono M, Kono M, Ohnishi N, Sato T, Tarumi M, Yoshimura M, Sato T, Karino K, Shimizu Y, Fujieda Y, Kato M, Hasebe R, Oku K, Murakami M, Atsumi T.
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Journal Title
Br J Haematol.
Volume: 196
Issue: 5
Pages: 1194-1204
DOI
Related Report
Peer Reviewed
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[Presentation] Rhodobacter azotoformans LPS is a TLR4 agonist that suppresses cytokine storm and enhances TLR3-mediated chemokine expression2021
Author(s)
Kaoru Murakami, Daisuke Kamimura, Rie Hasebe, Mona Uchida, Nobuya Abe, Reiji Yamamoto, Jing-Jing Jiang, Hiroki Tanaka, Shizuo Akira, Yuki Tanaka, Masaaki Murakami
Organizer
第50回日本免疫学会学術集会
Related Report
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[Presentation] Chronic stress-induced microglial interleukin-12/23 axis and medial prefrontal cortex impairment in neuropsychiatric lupus.2021
Author(s)
Nobuya Abe, Yuichiro Fujieda, Kenji Oku, Nobuhiko Takahashi, Kohei Karino, Mona Uchida, Michihito Kono, Yuki Tanaka, Rie Hasebe, Masaru Kato, Tatsuya Atsumi, Masaaki Murakami
Organizer
第50回日本免疫学会学術集会
Related Report
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