Development of fluorescence imaging technology for central catecholamines

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04029
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: The University of Tokyo
• Principal Investigator: Hirose Kenzo 東京大学, 大学院医学系研究科(医学部), 教授 (00292730)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: カテコラミン / シナプス / 蛍光イメージング

Outline of Final Research Achievements

The research aimed at developing fluorescence probes for visualization of the spatiotemporal dynamics of catecholamines in the brain, which are important neurotransmitters that control brain functions. In order to develop catecholamine-binding domain for fluorescence probes, we decided to obtain anti-catecholamine antibodies and convert them to single-chain fragments. We performed molecular design and organic synthesis of catecholamine derivatives and provided them for the production of immunoconjugates. A large number of hybridomas were obtained after treatment of mice with the conjugates, and antibodies binding to catecholamines were found through subsequent screening. However, a problem with their binding selectivity to physiological catecholamines has also been revealed. The findings obtained in this research are expected to be useful for future development of promising fluorescent probes.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

脳内カテコラミンを可視化する蛍光プローブの開発により、いつどこでカテコラミンが上昇するのかを生きた動物の脳において可視化が実現されるようになる。カテコラミンの関与する神経機能の解析にとって今後非常に重要なツールとして役立つと考えられる。特に、カテコラミンの関与する神経機能を時空間的コンテクストで理解を提供できる点で疾病の理解、創薬を目指す上でも大きな意義を持つ。本研究で得た知見は、今後の有望な蛍光プローブの開発に役立つと期待できる。