Fluorescence Probe for Imaging N-Methyl-d-aspartate Receptors and Monitoring GSH Selectively Using Two-Photon Microscopy

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Abstract
N-Methyl-d-aspartate (NMDA) is an excitotoxic amino acid used to identify a specific subset of glutamate receptors. The activity of NMDA receptors is closely related to the redox level of the biological system. Glutathione (GSH) as an antioxidant plays a key role with regard to modulation of the redox environment. In this work we designed and developed a GSH-specific fluorescent probe with the capability of targeting NMDA receptors, which was composed of a two-photon naphthalimide fluorophore, a GSH-reactive group sulfonamide, and an ifenprodil targeting group for the NMDA receptor. This probe exhibited high selectivity toward GSH in comparison to other similar amino acids. Two-photon fluorescence microscopy allowed this probe to successfully monitor GSH in neuronal cells and hippocampal tissues with an excitation at 750 nm. It could serve as a potential practical imaging tool to explore the function of GSH and related biological processes in the brain.
Funding Information
  • National Research Foundation of Korea (2012R1A3A2048814, 2019R1A2B5B03100278)
  • National Natural Science Foundation of China (21676113, 21772054)

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