Two-photon fluorescence imaging and specifically biosensing of norepinephrine on a 100-ms timescale

Leiwen Mao, Yujie Han, Qi-Wei Zhang () and Yang Tian ()
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Leiwen Mao: East China Normal University
Yujie Han: East China Normal University
Qi-Wei Zhang: East China Normal University
Yang Tian: East China Normal University

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract Norepinephrine (NE) is a key neurotransmitter in the central nervous system of organisms; however, specifically tracking the transient NE dynamics with high spatiotemporal resolution in living systems remains a great challenge. Herein, we develop a small molecular fluorescent probe that can precisely anchor on neuronal cytomembranes and specifically respond to NE on a 100-ms timescale. A unique dual acceleration mechanism of molecular-folding and water-bridging is disclosed, which boosts the reaction kinetics by ˃105 and ˃103 times, respectively. Benefiting from its excellent spatiotemporal resolution, the probe is applied to monitor NE dynamics at the single-neuron level, thereby, successfully snapshotting the fast fluctuation of NE levels at neuronal cytomembranes within 2 s. Moreover, two-photon fluorescence imaging of acute brain tissue slices reveals a close correlation between downregulated NE levels and Alzheimer’s disease pathology as well as antioxidant therapy.

Date: 2023
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DOI: 10.1038/s41467-023-36869-3

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