RNA-seq based transcriptome analysis on novel mechanism(s) of learning and memory

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K15991
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Kanazawa University
• Principal Investigator: Ishimoto Takahiro 金沢大学, 薬学系, 助教 (00843062)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 記憶学習 / 網羅的トランスクリプトーム解析 / 海馬歯状回特異的遺伝子発現抑制 / 神経突起伸長

Outline of Final Research Achievements

Comprehensive RNA-sequencing (RNA-seq) analysis of transcriptomes of hippocampal tissues in the mice showing cognitive enhancement by oral administration of a food-derived amino acid ergothioneine (ERGO) showed that some candidate mRNAs were significantly altered in the mice showing ERGO-induced cognitive enhancement. Moreover, ERGO administration significantly increased the expression level of a candidate molecule in the hippocampus, and inhibition of the candidate molecule diminished the ERGO-induced cognitive enhancement and neurogenesis. Additionally, the expression level of a candidate molecule in serum extracellular vesicles (EVs), which also contains brain-derived EVs, was significantly higher in volunteers treated with ERGO-containing tablets than in the placebo-treated group. Furthermore, the level in the serum EVs was significantly correlated with serum ERGO concentration and cognitive function.

Free Research Field

薬物治療学、神経薬理学

Academic Significance and Societal Importance of the Research Achievements

我が国の全人口に占める認知症患者の割合は世界で最も高く、その予防・治療薬の開発は喫緊の課題であるが、未だ根本治療薬はなくその開発は困難を極める。そこで安全性の高い食物由来成分の予防的摂取による戦略が考えられるが、我々は認知機能改善効果を示す食物由来アミノ酸ERGOに着目した。本課題では、ERGOの標的分子を網羅的トランスクリプトーム解析により見出し、さらには、血清中EVsにおいてある分子の発現がERGOの薬効バイオマーカーになり得る可能性を示唆した。発症の数十年前から病態が進行しているアルツハイマー病等の認知症におけるERGOの早期介入や予防的摂取により、病態の予防・遅延が可能かもしれない。