Linkage analysis of Cyclophilin D / Surtuin 3 signaling system in sepsis-associated brain dysfunction

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18307
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Tokyo Medical University
• Principal Investigator: Ishida Yusuke 東京医科大学, 医学部, 講師 (40805884)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 敗血症 / シクロフィリンD / 敗血症性関連脳傷害 / ミトコンドリア

Outline of Final Research Achievements

We investigated the role of brain mitochondria, CypD, MPT and SIRT3 signaling pathways in septic encephalopathy-induced brain cytokine expression, neuronal cell death and apoptosis formation. We created a model of septicemia-related brain injury induced by ileal ligation plus two punctures (CLP) using male C57B6 wild mice (wild group) and CypD gene-deficient (Ppif-/-) mice (CypD KO group) at 8-10 weeks of age. Cerebrum was sampled at 1, 6 hours, and 1 day after model creation for metabolomic and DNA chip analysis. We compared the activities of metabolites of various signaling pathways and examined the mechanisms leading to septic encephalopathy. Based on the data obtained, we are preparing to write a paper.

Free Research Field

神経麻酔、集中治療

Academic Significance and Societal Importance of the Research Achievements

研究成果としては、メタボローム解析や、ＤＮＡチップ解析から、敗血症性脳症誘発における脳内のミトコンドリア・CypD・MPT とSyvn・ERAD情報伝達系とオートファジーの役割が明確化され、SAE誘発性脳障害におけるミトコンドリア‐ER制御機構の役割の特定と、他の神経系関連疾患の病態解明にも貢献し新規治療薬開発へ繋がることが本研究の社会的意義と考える。