Analysis on novel mechanism(s) of learning and memory and evaluation of cognitive function using brain-derived exosomes in plasma

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23797
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Ishimoto Takahiro 金沢大学, 薬学系, 助教 (00843062)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 記憶学習 / 脳由来エクソソーム / バイオマーカー

Outline of Final Research Achievements

Ergothioneine (ERGO) is known to enhance cognitive function in human. Proteome analysis in mice showed oral administration of ERGO remarkably increased several proteins in hippocampal dentate gyrus (DG). Knockdown of a candidate protein in murine hippocampal DG by adeno-associated virus significantly enhanced neurite outgrowth, which may be one of the mechanisms underlying cognitive enhancement by ERGO.
Protein expression profile on exosomes derived from the brain in plasma may reflect the ERGO-induced enhancement of cognitive function. Expression of a candidate protein on exosomes in serum was associated with ERGO exposure and cognitive function, which might be a possible biomarker for assessment of ERGO-induced beneficial activity in the human brain.

Free Research Field

神経薬理学、薬物治療学

Academic Significance and Societal Importance of the Research Achievements

ヒトの認知機能を改善させるERGOの作用機序として、記憶を司る海馬歯状回におけるある候補蛋白質による神経突起の伸長が関与する可能性を示唆した。
認知機能の判定には、実験動物では行動試験、ヒトでは種々の認知機能検査が必要であるが、心理的要因などによるデータのばらつきが問題となり、より定量的な指標の確立が求められている。本研究で見出した脳内環境を反映する脳由来エクソソーム内の分子が、認知機能の改善を推測するバイオマーカーになる可能性がある。