Simultaneous Fluorescence Imaging Reveals N -Methyl-d-aspartic Acid Receptor Dependent Zn 2+ /H + Flux in the Brains of Mice with Depression

• Published in: Analytical chemistry (Washington) 2020-03, Vol.92 (5), p.4101-4107
• Main Authors: Wang, Xin, Bai, Xiaoyi, Su, Di, Zhang, Yandi, Li, Ping, Lu, Shuyi, Gong, Yulin, Zhang, Wen, Tang, Bo
• Format: Article
• Language: English
• Subjects: Animals; Brain - metabolism; Corticosterone - therapeutic use; Depression - drug therapy; Depression - metabolism; Depression - pathology; Disease Models, Animal; Fluorescent Dyes - chemical synthesis; Fluorescent Dyes - chemistry; Hydrogen - metabolism; Hydrogen-Ion Concentration; Ions - chemistry; Mice; Mice, Inbred C57BL; Microscopy, Confocal - methods; Oxidative Stress; PC12 Cells; Rats; Receptors, N-Methyl-D-Aspartate - metabolism; Zinc - metabolism
• ISSN: 0003-2700; 1520-6882
• DOI: 10.1021/acs.analchem.9b05771

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.