Molecular mechanisms of pathological modification by altered psychiatric states

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19364
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Murakami Masaaki 北海道大学, 遺伝子病制御研究所, 教授 (00250514)
• Project Period (FY): 2021-07-09 – 2023-03-31
• 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

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.

Free Research Field

免疫学, 炎症学, 神経免疫学

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。