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, People's Republic of China.
Anal Chem. 2020 Mar 3;92(5):4101-4107. doi: 10.1021/acs.analchem.9b05771. Epub 2020 Feb 24.
Depression is immensely attributed to the overactivation of -methyl-d-aspartic acid (NMDA) receptor in the brains. As regulatory binding partners of NMDA receptor, both Zn and H are intimately interrelated to NMDA receptor's activity. Therefore, exploring synergistic changes on the levels of Zn and H in brains will promote the knowledge and treatment of depression. However, the lack of efficient, appropriate imaging tools limits simultaneously tracking Zn and H in living mouse brains. Thus, a well-designed dual-color fluorescent probe (DNP) was fabricated for the simultaneous monitoring of Zn and H in the brains of mice with depression. Encountering Zn, the probe evoked bright blue fluorescence at 460 nm. Meanwhile, the red fluorescence at 680 nm was decreased with H addition. With blue/red dual fluorescence signal of DNP, we observed the synchronous increased Zn and H in PC12 cells under oxidative stress. Notably, imaging for the first time revealed the simultaneous reduction of Zn and pH in brains of mice with depression-like behaviors. Further results implied that the NMDA receptor might be responsible for the coinstantaneous fluctuation of Zn and H during depression. Altogether, this work is conducive to the knowledge of neural signal transduction mechanisms, advancing our understanding of the pathogenesis in depression.
抑郁症极大地归因于大脑中 -甲基-D-天冬氨酸（NMDA）受体的过度激活。作为 NMDA 受体的调节结合伴侣，Zn 和 H 都与 NMDA 受体的活性密切相关。因此，探索大脑中 Zn 和 H 水平的协同变化将促进对抑郁症的认识和治疗。然而，缺乏有效的、合适的成像工具限制了在活体小鼠大脑中同时追踪 Zn 和 H。因此，设计了一种双色荧光探针（DNP），用于同时监测抑郁小鼠大脑中的 Zn 和 H。与 Zn 相遇时，探针在 460nm 处发出明亮的蓝色荧光。同时，随着 H 的加入，680nm 处的红色荧光减少。通过 DNP 的蓝/红双荧光信号，我们观察到在氧化应激下 PC12 细胞中 Zn 和 H 的同步增加。值得注意的是，首次成像揭示了具有抑郁样行为的小鼠大脑中 Zn 和 pH 的同时减少。进一步的结果表明，NMDA 受体可能是抑郁症期间 Zn 和 H 同时波动的原因。总之，这项工作有助于了解神经信号转导机制，增进我们对抑郁症发病机制的理解。
