Cyclopaedically analyzing of drug target for Postoperative Cognitive Dysfunction by human cerebral spinal fluid proteome

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16468
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Mie University
• Principal Investigator: Nakamori Yuki 三重大学, 医学部附属病院, 助教 (80815994)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: POCD / 全身麻酔後認知機能障害 / 術後認知機能障害 / プロテオミクス / プロテオーム / 脳脊髄液 / SWATH / DIA

Outline of Final Research Achievements

This research performed proteomics analysis of time-sequential human cerebrospinal fluid(CSF). The protein concentration of CSF is not as rich as blood, therefore this research established preprocessing method using Amicon Ultra (Merck Inc.) for ultrafiltration and Pierce Albumin/IgG Removal Kits (Thermo Fisher Scientific Inc.) for removing abundant proteins. Using this method, proteins of CSF were detected. Furthermore, multiple proteomics techniques including two-dimensional electrophoresis and iTRAQ (isobaric Tags for Relative and Absolute Quantitation) were tested and all of them could show time-sequential relative protein amount change.

Free Research Field

集中治療医学

Academic Significance and Societal Importance of the Research Achievements

術後認知機能障害(POCD: Postoperative Cognitive Dysfunction)は、高齢者に多くみられる脳障害の1つである。POCD発症患者は、術後入院期間が長く、長期生存率も低いことが知られているが、どのようなメカニズムで長期にわたり障害を及ぼすのか不明である。このような重要な問いに対し、ヒト脳脊髄液(CSF)という貴重な臨床サンプルの経時的なプロテオミクスからのアプローチで病態の主因となりうるタンパクを探索した。また、血液と比較して経験が乏しくタンパク濃度がはるかに薄いCSFでもプロテオーム解析を実現すべく、前処理方法を模索し確立した。