Light sleep, the more you sleep, the more tired you are?

Sleep, a physiological activity anchored in human genes, accounts for one-third of human life
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According to the World Health Organization survey, about 27% of the world's population has sleep disorders, and in China, the incidence of adult insomnia is as high as 38%! According to the "2022 China Healthy Sleep Survey White Paper" released by the China Sleep Research Association in 2022, nearly three-quarters of people have experienced sleep disturbances, and difficulty falling asleep has become the number one problem
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Among them, the average sleep time for minors is only 7 hours; for people between the ages of 25 and 60, the sleep time gradually decreases with age, and the proportion of sleep time exceeds 6 hours gradually decreases - for young adults, "sleep time" "Not good" can be mainly attributed to "high pressure"; and for the elderly, poor health may be the main reason for affecting sleep
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(Source: China Sleep Research Association) In addition to sleep duration, sleep quality also affects our sleeping experience
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We often have the "disorienting experience" of waking up exhausted after a long sleep
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This is because there is not enough deep sleep
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As an important part of sleep, deep sleep is called "golden sleep", accounting for 25% of the entire sleep time.
It can relieve people's fatigue for a day, promote the metabolism of the human body, and is of great benefit to the body
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So how does the brain regulate the human body to enter deep sleep? Scientists have been working on this problem for years in an attempt to find effective ways to alleviate sleep problems
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A recent study published in Nature Communications by researchers at Harvard Medical School provides a key clue to this long-standing mystery: they found that knocking out the GABAA alpha3 subunit on thalamic reticular neurons effectively enhanced mouse of deep sleep
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(Image source: Nature Communications) As we all know, sleep can be mainly divided into two types, one is rapid eye movement sleep (REM sleep) and the other is non-rapid eye movement sleep (NREM sleep)
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The REM sleep stage is the most important period of dreaming; the stages other than REM sleep are collectively referred to as NREM sleep
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According to the depth of sleep, NREM sleep can be divided into stage 1, stage 2 and stage 3
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Stages 1 and 2 are collectively referred to as "light sleep," and stage 3 is called "deep sleep
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When entering deep sleep, deep and slow brain waves called "delta waves" begin to appear in the brain.
At this stage, noise and activity may not respond to people, which is usually called "sleep
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Changes in sleep stages throughout the night (Credit: Internet) The research team focused on neurons in the thalamus, an area of ​​the brain responsible for regulating functions such as sleep and wakefulness
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Using gene editing techniques, the researchers disrupted a protein that encodes a protein that binds inhibitory neurotransmitters, GABAA—a family of proteins that are targeted by sleeping pills, commonly used sleeping pills such as non-benzodiazepines and benzodiazepines ) can improve sleep by activating GABAA receptors
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However, activated GABAA activity reduced delta oscillations, suggesting that GABAA receptors prevent the human body from entering deep sleep, that is, sleeping pills do not lead to high-quality sleep
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In this study, the researchers knocked out the GABAA α3 gene in the mouse thalamus (because the α3 isoform is predominant in the thalamic reticularis) to study the effect of GABAA receptors on thalamic reticular neurons on delta oscillations in NREM.
influence to reflect the quality of deep sleep
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Interestingly, α3 knockout mice had higher NREM Delta oscillatory power compared to baseline (BL) recordings
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NREM Delta Oscillation Power (Source: Nature Communications) In humans, delta oscillations are most prominent in N3, the deepest stage of NREM sleep, and arousal thresholds also increase with the depth of NREM sleep
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Given that humans are more likely to wake up from the lighter N1 or N2 phases, the researchers analyzed the delta oscillations preceding the NREM → REM and NREM → wake transitions
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Unexpectedly, the researchers found that after α3 knockout, the delta oscillation was only significantly increased during the NREM → REM period; while there was no significant difference between NREM → pre-awake
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Delta power (Image source: Nature Communications) In addition, before the transition to REM, the delta oscillation frequency remained at a high level throughout the NREM cycle, and GABAA α3 was suppressed and the delta oscillation level was higher
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There is also a significant linear relationship in this process: with the longer NREM duration at the NREM→REM transition, the greater the increase in the delta oscillation frequency
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That got the researchers excited
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To reconfirm that this improvement in deep sleep was due to inhibition of the GABAA α3 subunit, they performed histological examination of the reticular nucleus of the thalamus and determined that GABAA α3 was indeed knocked out in most regions of the thalamus
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From this, the researchers came to an important conclusion that the inhibition of the GABAA α3 gene in the reticular nucleus of the thalamus determines the increase in delta oscillatory power during NREM and induces deep sleep in the body
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Cas9-sgRNA distribution detection (Source: Nature Communications) Although the currently commonly used sleeping pills have good efficacy in the treatment of insomnia, they also have well-known drawbacks: many drugs make people fall asleep quickly, but at the same time inhibit the brain's restorative Delta wave activity.
Taking sleeping pills to fall asleep is not necessarily restorative, and the quality of sleep will be greatly reduced
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"Our findings represent an important step in pinpointing the molecular basis of sleep regulation and point to an alternative pharmaceutical strategy for promoting natural, restorative sleep," said senior researcher Radhika Basheer.
"We believe our The findings lay the groundwork for the development of a new sleep drug that could achieve the maintenance of deep sleep critical to deep sleep by promoting delta wave oscillations
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"Life is in deep sleep
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It is hoped that this new type of sleeping pill will be developed as soon as possible, so that people with sleep disorders can also have a fast and sweet "spring" ~ Reference [1] Uygun DS, Yang C, Tilli ER, Katsuki F, Hodges EL, McKenna JT , McNally JM, Brown RE, Basheer R.
Knockdown of GABAA alpha3 subunits on thalamic reticular neurons enhances deep sleep in mice.
Nat Commun.
2022 Apr 26;13(1):2246.
doi: 10.
1038/s41467-022-29852-x .
‍Written | Edited by Le Yi | Swagpp Click "read the original text" below to download the Mace Medical APP