An antagonist-based two-photon fluorogenic probe for imaging metabotropic glutamate receptor 5 in neuronal cells

Mingran Si; Xinyi Cai; Yani Liu; Zheng Li; Xiangjie Luo; Hai-Liang Zhu; Yong Qian

doi:10.1016/j.talanta.2024.126167

An antagonist-based two-photon fluorogenic probe for imaging metabotropic glutamate receptor 5 in neuronal cells

Talanta. 2024 May 1:275:126167. doi: 10.1016/j.talanta.2024.126167. Online ahead of print.

Authors

Mingran Si¹, Xinyi Cai², Yani Liu², Zheng Li¹, Xiangjie Luo³, Hai-Liang Zhu⁴, Yong Qian⁵

Affiliations

¹ Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, China.
² State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Xianlin Road 163, Nanjing, 210023, China.
³ Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, China. Electronic address: xiangjieluo@qq.com.
⁴ State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Xianlin Road 163, Nanjing, 210023, China. Electronic address: zhuhl@nju.edu.cn.
⁵ Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, China. Electronic address: yongqian@njnu.edu.cn.

PMID: 38710128
DOI: 10.1016/j.talanta.2024.126167

Abstract

The expression of metabotropic glutamate receptor 5 (mGluR5) is subject to developmental regulation and undergoes significant changes in neuropsychiatric disorders and diseases. Visualizing mGluR5 by fluorescence imaging is a highly desired innovative technology for biomedical applications. Nevertheless, there are substantial problems with the chemical probes that are presently accessible. In this study, we have successfully developed a two-photon fluorogenic probe, mGlu-5-TP, based on the structure of mGluR5 antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP). Due to this antagonist-based probe selectively recognizes mGluR5, high expression of mGluR5 on living SH-SY5Y human neuroblastoma cells has been detected during intracellular inflammation triggered by lipopolysaccharides (LPS). Of particular significance, the probe can be employed along with two-photon fluorescence microscopy to enable real-time visualization of the mGluR5 in Aβ fiber-treated neuronal cells, thereby establishing a connection to the progression of Alzheimer's disease (AD). These results revealed that the probe can be a valuable imaging tool for studying mGluR5-related diseases in the nervous system.

Keywords: Bioimaging; Metabotropic glutamate receptor 5; Neuropsychiatric diseases; Two-photon fluorescent probe.