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

Area of Science:

• Biochemistry
• Neuroscience
• Molecular Biology

Background:

• Lithium is a long-standing treatment for bipolar disorder (BD).
• Its therapeutic use is constrained by a narrow therapeutic window (0.6–1.2 mM).
• Understanding lithium ion (Li+) cellular distribution is crucial for optimizing its use, but selective in vivo imaging remains a challenge.

Purpose of the Study:

• To develop a highly selective fluorescent sensor for Li+ imaging in living cells.
• To investigate the cellular distribution of Li+ in cells derived from bipolar disorder patients and healthy controls.

Main Methods:

• In vitro selection and development of a DNAzyme-based fluorescent sensor with high Li+ selectivity (>100-fold over other metal ions).
• Comparative visualization of Li+ in HeLa cells, human neuronal progenitor cells (NPCs), and differentiated neurons from BD patients and healthy controls.

Main Results:

• The developed DNAzyme sensor demonstrated high selectivity for Li+.
• Enhanced accumulation of Li+ was observed in differentiated neurons derived from BD patients compared to healthy controls.
• No significant difference in Li+ accumulation was found in neuronal progenitor cells (NPCs) between the two groups.

Conclusions:

• The DNAzyme-based sensor provides a novel platform for biomedical research, enabling selective Li+ visualization in cellular models.
• Findings suggest differential Li+ accumulation in neurons of BD patients, potentially impacting lithium drug response.
• This technology can advance research into BD pathophysiology and lithium drug mechanisms.