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一种用于可视化急性癫痫小鼠大脑中乙酰胆碱酯酶通量的近红外荧光探针。

A Near-Infrared Fluorescent Probe for Visualization of Acetylcholinesterase Flux in the Acute Epileptic Mice Brain.

作者信息

Fan Li, Wang Rui, Zan Qi, Zhao Kunyi, Zhang Yuewei, Huang Yunong, Yu Xue, Yang Yongming, Lu Wenjing, Shuang Shaomin, Yang Xihua, Dong Chuan

机构信息

Institute of Environmental Science, School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, People's Republic of China.

School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, China.

出版信息

Chem Biomed Imaging. 2024 Oct 17;3(5):332-340. doi: 10.1021/cbmi.4c00058. eCollection 2025 May 26.

Abstract

Neurotransmitter imbalance is an important pathological basis for epilepsy seizures. Acetylcholinesterase (AChE) as a key hydrolase in the cholinergic system directly affects the metabolism of neurotransmitter. Unfortunately, owing to the lack of reliable in situ imaging tools in the brain, the association between AChE and epilepsy has not been fully elucidated yet. Here, we rationally designed a near-infrared (NIR) fluorescent probe () by employing ,-dimethyl carbamyl as an AChE sensing group in the quinolinium-xanthene NIR skeleton. exhibited high sensitivity, excellent selectivity, and ultrafast response time (within 0.5 s) toward AChE. Moreover, can sensitively monitor the fluctuations of AChE activity in the neuronal cells and zebrafish during the apoptosis or oxidative stress process. Significantly, using with superb blood-brain barrier (BBB) permeability, for the first time, we discovered a down-regulated AChE level in the acute epileptic mice brain through noninvasive NIR in vivo imaging. Moreover, the visualization of therapeutic evaluation of epilepsy has also been achieved by monitoring AChE with . This work demonstrated the great potential of as an effective imaging tool for epilepsy diagnosis, therapeutic evaluation, and pathogenesis study.

摘要

神经递质失衡是癫痫发作的重要病理基础。乙酰胆碱酯酶(AChE)作为胆碱能系统中的关键水解酶,直接影响神经递质的代谢。遗憾的是,由于缺乏可靠的脑内原位成像工具,AChE与癫痫之间的关联尚未完全阐明。在此,我们通过在喹啉 - 呫吨近红外骨架中采用N,N - 二甲基氨基甲酰基作为AChE传感基团,合理设计了一种近红外(NIR)荧光探针()。该探针对AChE表现出高灵敏度、优异的选择性和超快响应时间(在0.5秒内)。此外,该探针能够灵敏地监测神经元细胞和斑马鱼在凋亡或氧化应激过程中AChE活性的波动。值得注意的是,利用具有出色血脑屏障(BBB)通透性的该探针,我们首次通过无创近红外体内成像发现急性癫痫小鼠脑内AChE水平下调。此外,通过用该探针监测AChE,还实现了癫痫治疗评估的可视化。这项工作证明了该探针作为癫痫诊断、治疗评估和发病机制研究的有效成像工具具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a48/12117416/b75d46ecc65a/im4c00058_0007.jpg

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