DNAzyme-Based Lithium-Selective Imaging Reveals Higher Lithium Accumulation in Bipolar Disorder Patient-Derived Neurons
| Autor: | K. Sue O'Shea, Yi Lu, Shanni Hong, Claire E. McGhee, Yuting Wu, Cynthia J. DeLong, Weijie Guo, Yuan Ma, Mingkuan Lyu, Zhenglin Yang, Melvin G. McInnis |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | ACS Central Science ACS Central Science, Vol 7, Iss 11, Pp 1809-1820 (2021) |
| ISSN: | 2374-7951 2374-7943 |
| Popis: | Lithium has been a drug for bipolar disorders (BD) for over 70 years; however, its usage has been limited by its narrow therapeutic window (between 0.6 and 1.2 mM). Understanding the cellular distribution of lithium ions (Li+) in patient cells will offer deep insight into this limitation, but selective imaging of Li+ in living cells under biomedically relevant concentration ranges has not been achieved. Herein, we report in vitro selection and development of a Li+-specific DNAzyme fluorescent sensor with >100-fold selectivity over other biorelevant metal ions. This sensor allows comparative Li+ visualization in HeLa cells, human neuronal progenitor cells (NPCs), and neurons derived from BD patients and healthy controls. Strikingly, we detected enhanced accumulation of Li+ in cells derived from BD patients compared with healthy controls in differentiated neurons but not NPCs. These results establish the DNAzyme-based sensor as a novel platform for biomedical research into BD and related areas using lithium drugs. A highly Li+ selective DNAzyme sensor for live imaging of Li+ at a biomedical relevant concentration range reveals bipolar disorder patient-derived neurons can accumulate more Li+ than healthy neurons can. |
| Databáze: | OpenAIRE |
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