DNAzyme-Based Lithium-Selective Imaging Reveals Higher Lithium Accumulation in Bipolar Disorder Patient-Derived Neurons

Claire E. McGhee, Zhenglin Yang, Weijie Guo, Yuting Wu, Mingkuan Lyu, Cynthia J. Delong, Shanni Hong, Yuan Ma, Melvin G. McInnis, K. Sue O'Shea, Yi Lu

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1809-1820
Number of pages12
JournalACS Central Science
Volume7
Issue number11
Early online dateNov 3 2021
DOIs
StatePublished - Nov 24 2021

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering

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