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, Shandong Normal University, Jinan 250014, P. R. China.
School of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo 255049, P. R. China.
Analyst. 2018 Dec 17;144(1):191-196. doi: 10.1039/c8an01626g.
Depression is a common mental illness with high morbidity and mortality. Mounting evidence suggests that an imbalance of the oxidant-antioxidant defence system is strongly correlated with depression and the dysfunction of the endoplasmic reticulum (ER) is strongly related to the oxidative stress. Therefore, as vital and abundant antioxidants in the ER, biothiols may contribute to the etiology of depression. However, ideal two-photon (TP) fluorescent probes for in vivo imaging of ER-associated thiols in the brains of mice with depression phenotypes are still lacking. Hence, we describe a fluorescent probe (ER-SH) to visualize thiols in living systems. ER-SH displays high sensitivity, excellent ER-targeting ability, outstanding TP properties and low cytotoxicity. Using this ER-SH probe, we succeeded in revealing an increase in the endogenous thiol levels under ER stress induced by DTT. Significantly, TP in vivo imaging showed for the first time that the thiol levels are reduced in brains of mice with depression phenotypes. Collectively, this work can assist in further understanding the molecular mechanism of depression and offers a crucial dimension for diagnosis and anti-depression treatments.
抑郁症是一种常见的精神疾病，具有较高的发病率和死亡率。越来越多的证据表明，氧化还原防御系统的失衡与抑郁症密切相关，内质网（ER）功能障碍与氧化应激密切相关。因此，作为 ER 中重要且丰富的抗氧化剂，生物硫醇可能有助于抑郁症的发病机制。然而，用于在具有抑郁表型的小鼠大脑中进行 ER 相关硫醇的体内成像的理想的双光子（TP）荧光探针仍然缺乏。因此，我们描述了一种用于在活系统中可视化硫醇的荧光探针（ER-SH）。ER-SH 具有高灵敏度、优异的 ER 靶向能力、出色的 TP 特性和低细胞毒性。使用这种 ER-SH 探针，我们成功地揭示了 DTT 诱导的 ER 应激下内源性硫醇水平的增加。重要的是，TP 体内成像首次显示出抑郁表型小鼠大脑中的硫醇水平降低。总的来说，这项工作有助于进一步了解抑郁症的分子机制，并为诊断和抗抑郁治疗提供了一个重要的维度。
