• Lithium imaging method could shine new l

    From ScienceDaily@1:317/3 to All on Wed Nov 3 21:30:52 2021
    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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