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

IF 5.6 1区化学 Q1 CHEMISTRY, ANALYTICAL Talanta Pub Date : 2024-08-01 Epub Date: 2024-05-01 DOI:10.1016/j.talanta.2024.126167

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

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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.

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一种基于拮抗剂的双光子荧光探针，用于对神经细胞中的代谢谷氨酸受体 5 进行成像。

代谢型谷氨酸受体 5（mGluR5）的表达受发育调控，并在神经精神障碍和疾病中发生显著变化。通过荧光成像可视化 mGluR5 是生物医学应用中一项备受期待的创新技术。然而，目前可获得的化学探针存在很多问题。在这项研究中，我们基于 mGluR5 拮抗剂 6-甲基-2-（苯乙炔基）吡啶（MPEP）的结构，成功开发了一种双光子荧光探针 mGlu-5-TP。由于这种基于拮抗剂的探针能选择性地识别 mGluR5，因此在脂多糖（LPS）引发的细胞内炎症过程中，活体 SH-SY5Y 人神经母细胞瘤细胞上 mGluR5 的高表达被检测到。特别重要的是，该探针可与双光子荧光显微镜一起使用，实时观察经 Aβ 纤维处理的神经细胞中的 mGluR5，从而建立与阿尔茨海默病（AD）进展的联系。这些结果表明，该探针是研究神经系统中与mGluR5相关疾病的重要成像工具。

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来源期刊

Talanta 化学-分析化学

CiteScore

12.30

自引率

4.90%

发文量

861

审稿时长

29 days

期刊介绍： Talanta provides a forum for the publication of original research papers, short communications, and critical reviews in all branches of pure and applied analytical chemistry. Papers are evaluated based on established guidelines, including the fundamental nature of the study, scientific novelty, substantial improvement or advantage over existing technology or methods, and demonstrated analytical applicability. Original research papers on fundamental studies, and on novel sensor and instrumentation developments, are encouraged. Novel or improved applications in areas such as clinical and biological chemistry, environmental analysis, geochemistry, materials science and engineering, and analytical platforms for omics development are welcome. Analytical performance of methods should be determined, including interference and matrix effects, and methods should be validated by comparison with a standard method, or analysis of a certified reference material. Simple spiking recoveries may not be sufficient. The developed method should especially comprise information on selectivity, sensitivity, detection limits, accuracy, and reliability. However, applying official validation or robustness studies to a routine method or technique does not necessarily constitute novelty. Proper statistical treatment of the data should be provided. Relevant literature should be cited, including related publications by the authors, and authors should discuss how their proposed methodology compares with previously reported methods.