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利用双光子荧光成像技术研究具有抑郁表型的小鼠大脑中羟自由基的功能。

Illuminating the Function of the Hydroxyl Radical in the Brains of Mice with Depression Phenotypes by Two-Photon Fluorescence Imaging.

机构信息

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for, Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University, Jinan, 250014, P. R. China.

出版信息

Angew Chem Int Ed Engl. 2019 Mar 26;58(14):4674-4678. doi: 10.1002/anie.201901318. Epub 2019 Feb 27.

Abstract

Depression is intimately linked with oxidative stress. As one of the most reactive and oxidative reactive oxygen species that is overproduced during oxidative stress, the hydroxyl radical ( OH) can cause macromolecular damage and subsequent neurological diseases. However, due to the high reactivity and low concentration of OH, precise exploration of OH in brains remains a challenge. The two-photon fluorescence probe MD-B was developed for in situ OH imaging in living systems. This probe achieves exceptional selectivity towards OH through the one-electron oxidation of 3-methyl-pyrazolone as a new specific recognition site. MD-B can be used to map OH in mouse brain, thereby revealing that increased OH is positively correlated with the severity of depression phenotypes. Furthermore, OH has been shown to inactivate deacetylase SIRT1, thereby leading to the occurrence and development of depression phenotypes. This work provides a new strategy for the future treatment of depression.

摘要

抑郁症与氧化应激密切相关。作为氧化应激过程中产生的最具反应性和氧化活性的活性氧物种之一,羟基自由基(OH)会导致大分子损伤和随后的神经退行性疾病。然而,由于 OH 的高反应性和低浓度,精确探测大脑中的 OH 仍然是一个挑战。双光子荧光探针 MD-B 被开发用于活系统中 OH 的原位成像。该探针通过作为新的特定识别位点的 3-甲基-吡唑啉酮的单电子氧化实现对 OH 的卓越选择性。MD-B 可用于在小鼠大脑中绘制 OH,从而揭示增加的 OH 与抑郁表型的严重程度呈正相关。此外,OH 已被证明会使去乙酰化酶 SIRT1 失活,从而导致抑郁表型的发生和发展。这项工作为未来抑郁症的治疗提供了一种新策略。

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