• Molecular basis of deep sleep pinpointed

    From ScienceDaily@1:317/3 to All on Friday, April 29, 2022 22:30:48
    Molecular basis of deep sleep pinpointed, suggests avenues for novel treatments

    Date:
    April 29, 2022
    Source:
    Harvard Medical School
    Summary:
    Scientists pinpoint the molecular epicenter of deep-sleep
    regulation. The findings, based on research in mice, identify a
    gene that makes a protein that regulates delta waves -- electrical
    signals between neurons that occur during the deepest phases of
    relaxation and are a hallmark of restorative sleep.



    FULL STORY ========================================================================== Healthy sleep is a basic physiologic need. In its absence, a myriad
    of processes in the body can go terribly awry. Chronic sleep problems
    have been linked to mental health disorders, cardiovascular disease,
    type 2 diabetes, and obesity, among other conditions.


    ==========================================================================
    Yet, consistently achieving the deep, restorative sleep necessary for
    optimal physiologic health and peak cognitive performance can be difficult
    due to lifestyle, environmental, and biologic factors.

    One of the most confounding questions in sleep biology has been how deep
    sleep is regulated by the brain. The answer could help illuminate new
    ways to mitigate sleep problems.

    Now, a newly published study led by Harvard Medical School researchers at
    VA Boston Healthcare Systemoffers critical clues into this longstanding mystery.

    The work, conducted in mice and published April 26 in Nature
    Communications, identifies an area in the brain that regulates the
    oscillations of delta waves -- electrical signals transmitted across
    neurons that arise during the deepest phases of relaxation. They are a
    hallmark of restorative sleep.

    The research team homed in on neurons in the thalamus, a region of the
    brain that regulates sleep and wakefulness, among other functions. Using CRISPR-Cas9 gene editing, the researchers disrupted a gene that codes for
    a protein that binds the inhibitory neurotransmitter GABA. The protein is
    a target of drugs that promote sleep. Disruption of this gene in mouse
    models boosted the activity of delta waves and enhanced deep sleep in
    the animals.



    ==========================================================================
    If replicated in further animal models, the findings could lay the
    groundwork for designing therapies that precision-target this protein
    to induce deep sleep.

    "Our findings represent an important step forward in pinpointing
    the molecular basis of sleep regulation and point to an alternative pharmacologic strategy for promoting natural, restorative sleep,"
    said study senior investigator Radhika Basheer, associate professor of psychiatry at HMS and VA Boston.

    New therapies are sorely needed. Commonly used insomnia medicines,
    while an important tool for treatment of persistent insomnia, have
    well-known drawbacks.

    Many of these medications work by getting people to fall asleep fast, but
    they also tend to dampen the activity of restorative delta waves. Thus,
    while such medications promote falling asleep, the slumber they induce
    is not necessarily restorative.

    "We believe our findings set the stage for developing a new class of sleep medicines that can achieve this all-important maintenance of deep sleep
    by boosting delta wave oscillations," added Basheer, who co-led the study
    with colleague Ritchie Brown, associate professor of psychiatry at HMS.

    HMS co-authors include David Uygun, Chun Yang, Fumi Katsuki, Erik Hodges,
    James McKenna, and James McNally. Elena Tilli of Stonehill College was
    also a co- author on the study.

    This work was supported by VA Biomedical Laboratory Research and
    Development Service Merit Awards and by National Institutes of Health
    grants R01 NS119227, R21 NS079866, R01 MH039683, T32 HL07901, K01
    AG068366, R21 MH125242.

    Disclosures: Uygun, McKenna, McNally, Brown, and Basheer are research
    health scientists at VA Boston Healthcare System. The contents of
    this work do not represent the views of the US Department of Veterans
    Affairs or the United States Government. McKenna received partial salary compensation and funding from Merck MISP (Merck Investigator Sponsored Programs) but has no conflict of interest with this work.


    ========================================================================== Story Source: Materials provided by Harvard_Medical_School. Original
    written by Ekaterina Pesheva. Note: Content may be edited for style
    and length.


    ========================================================================== Journal Reference:
    1. David S. Uygun, Chun Yang, Elena R. Tilli, Fumi Katsuki, Erik
    L. Hodges,
    James T. McKenna, James M. McNally, Ritchie E. Brown, Radhika
    Basheer.

    Knockdown of GABAA alpha3 subunits on thalamic reticular neurons
    enhances deep sleep in mice. Nature Communications, 2022; 13 (1)
    DOI: 10.1038/ s41467-022-29852-x ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220429145059.htm

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