Simultaneous Fluorescence Imaging Reveals N‑Methyl‑d‑aspartic Acid Receptor Dependent Zn2+/H+ Flux in the Brains of Mice with Depression

Depression is immensely attributed to the overactivation of N-methyl-d-aspartic acid (NMDA) receptor in the brains. As regulatory binding partners of NMDA receptor, both Zn2+ and H+ are intimately interrelated to NMDA receptor’s activity. Therefore, exploring synergistic changes on the levels of Zn2...

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Bibliographic Details
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:
Analytical chemistry
Aspartic acid
Chemistry
Fluorescence
Fluorescent indicators
Glutamic acid receptors (ionotropic)
Hydrogen
Imaging
N-Methyl-D-aspartic acid receptors
Oxidative stress
Pathogenesis
Pheochromocytoma cells
Signal transduction
Zinc
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Summary:Depression is immensely attributed to the overactivation of N-methyl-d-aspartic acid (NMDA) receptor in the brains. As regulatory binding partners of NMDA receptor, both Zn2+ and H+ are intimately interrelated to NMDA receptor’s activity. Therefore, exploring synergistic changes on the levels of Zn2+ and H+ in brains will promote the knowledge and treatment of depression. However, the lack of efficient, appropriate imaging tools limits simultaneously tracking Zn2+ and H+ in living mouse brains. Thus, a well-designed dual-color fluorescent probe (DNP) was fabricated for the simultaneous monitoring of Zn2+ and H+ in the brains of mice with depression. Encountering Zn2+, 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 Zn2+ and H+ in PC12 cells under oxidative stress. Notably, in vivo imaging for the first time revealed the simultaneous reduction of Zn2+ 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 Zn2+ 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.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.9b05771