Lithium imaging method could shine new light on bipolar disorder,
treatment

Date:
November 3, 2021
Source:
American Chemical Society
Summary:
Since 1949, lithium has been a mainstay for treating bipolar
disorder (BD), a mental health condition marked by extreme mood
swings. But scientists still don't have a clear understanding
of how the drug works, or why some patients respond better than
others. Now, researchers have developed a method for imaging lithium
in living cells, allowing them to discover that neurons from BD
patients accumulate higher levels of lithium than healthy controls.



FULL STORY ========================================================================== Since 1949, lithium has been a mainstay for treating bipolar disorder
(BD), a mental health condition marked by extreme mood swings. But
scientists still don't have a clear understanding of how the drug works,
or why some patients respond better than others. Now, researchers
reporting in ACS Central Sciencedeveloped a method for imaging lithium
in living cells, allowing them to discover that neurons from BD patients accumulate higher levels of lithium than healthy controls.


========================================================================== According to the National Institutes of Health, 4.4% of U.S. adults
experience BD at some time in their lives. Studies have shown that lithium-based drugs can help stabilize mood and reduce suicide risk in
people with BD. However, only about one-third of BD patients respond
completely to lithium treatment, and the rest respond only partially or
not at all. One reason could be that the drug has an extremely narrow therapeutic range: Below a certain blood serum level of lithium,
most patients do not respond, but at a slightly higher level, they
can experience severe side effects. Being able to measure lithium concentrations directly in a patient's neurons could help scientists
understand how lithium works as a drug, and then they could use this
knowledge to optimize the dosage.

So Yi Lu and colleagues wanted to develop a method to detect and measure lithium in living cells at therapeutically relevant concentrations.

The researchers used in vitro selection to identify a DNA enzyme (DNAzyme)
that catalyzes the release of a fluorescent molecule from an RNA probe,
thus producing a signal, only when lithium is present. The DNAzyme was 100 times more selective for lithium over other metal ions, such as sodium and potassium, that are present at much higher concentrations in human cells,
and it was sensitive enough to detect lithium at concentrations within
the therapeutic range. As a proof of concept, the researchers collected
skin cells from BD patients and healthy donors, reprogrammed them to
stem cells and then differentiated them into neurons. The team treated
the neurons with the DNAzyme-based sensor and a therapeutically relevant
dosage of lithium. Using fluorescence microscopy, the researchers found
that immature neurons from BD patients and healthy controls accumulated
similar levels of lithium, but mature neurons from BD patients accumulated higher levels of lithium than mature control neurons. The new lithium
sensor is a powerful tool to better understand the effects of lithium
in treating BD, the researchers say.

========================================================================== Story Source: Materials provided by American_Chemical_Society. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. 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. DNAzyme-Based Lithium-Selective Imaging Reveals
Higher Lithium Accumulation in Bipolar Disorder Patient-Derived
Neurons. ACS Central Science, 2021; DOI: 10.1021/acscentsci.1c00843 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211103082610.htm

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