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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