Medically reviewed by
Dacelin St Martin, MD
Triple board-certified in Sleep Medicine,
Internal Medicine, and Pediatrics.
What is Sleep? | Looking into the Numeric | Sleep Architecture | Homeostatic Sleep Pressure | Circadian Rhythm | Macromolecules & Sleep | The Nemuri Gene & Sleep
Introduction
There’s an undeniable case for sleep and its essential role in maintaining short and long-term health.
Empirically, we know that disturbed sleep makes us susceptible to acute and chronic illnesses by compromising our immunity.
Keep reading to find out more about sleep architecture and the physiological changes we experience when we’re sick.
What is Sleep?
Sleep is a behaviorally altered state of consciousness marked by a decreased responsivity to stimuli and the inhibition of voluntary movements.
There are multiple neural functions associated with sleep, such as providing support for changes in brain connectivity and related regulatory mechanisms.[1]
Looking into the Numeric
According to a study conducted by Ursin R. et al., the mean (±SD) nocturnal sleep duration during weekdays in men was 6 hours 52 minutes, and women 7 hours 11 minutes (±57 minutes).
Whereas mean subjective sleep need was found to be 7 hours 16 minutes (±52 minutes) in men; and 7 hours 45 minutes (±52 minutes) in women.
In total, these variables accounted for only around 3% of the variance in sleep duration and sleep needs. Ten percent of the men and 12.2% of the women reported frequent insomnia.[2]
However, no single measure identifies sleep; instead, it can be characterized experimentally by two or more behavioral or physiological correlations, including objective changes in brain activity, measured by electroencephalogram (EEG), nerve and muscle activity, measured by electromyogram (EMG), or respiratory rate.
Sleep Architecture
As characterized by an electroencephalogram (EEG), a test for brain activity, sleep comprises two major phases:
1) Non-rapid eye movement (NREM) Sleep, further subdivided into:
-
- N1: the process of change from being awake to being asleep
- N2: the onset of sleep, characterized by a low-voltage EEG, along with features of spindles and K-complexes
- N3 or slow-wave sleep (SWS): previously subdivided into stage 3 and stage 4 sleep, is characterized by a greater quantity of high-amplitude, low-frequency EEG components
2) Rapid eye movement (REM) Sleep is a stage of sleep characterized by the rapid movement of the eyes, low muscle tone throughout the body, and a tendency for vivid dreams.
Homeostatic Sleep Pressure
Sleep regulation involves a fundamental homeostatic process, whose strength is highly influenced by the length of the last sleep period.
The homeostatic pressure keeps increasing as long as the person stays awake. The longer the wake cycle, the stronger the homeostatic drive to sleep. Basically, the longer you’re awake, the more intense you’re urged will be to sleep.
This physiological reaction explains our increased drive to recover from the lost sleep, leading to shorter sleep latency and enhanced EEG synchrony in NREM sleep. Simply stated, you fall asleep faster and experience more deep sleep.
Circadian Rhythm
Secondly, to control the timing and organization of sleep, another process is involved, referred to as the circadian process, located in the suprachiasmatic nucleus (SCN) in the brain. A circadian timing mechanism heavily influences the timing of sleep.[3]
According to various studies conducted, it was found that “The circadian timing system” includes three different components: [4]
(1) Input pathways that transmit light and other signals to the circadian “clock” and thus entrain circadian rhythms to environmental cues, primarily the light-dark cycle
(2) An endogenous circadian pacemaker that generates rhythms having a period of approximately 24 hours
(3) Output pathways controlled by the pacemaker.
Macromolecules & Sleep
Apart from the above-discussed factors, humoral substances, such as lactic acid, blood sugar, carbon dioxide, and calcium, are also proved to be related to the mechanism of sleep.
Vasopressin, progesterone, testosterone, LH, lactogenic hormone, 4- hydroxy butyrate, and 5-HTP have been reported to be associated with the appearance of REM sleep, whereas a study conducted by Jouvet et al. found that slow-wave and REM sleep were possibly regulated by serotonin, a hormone that stabilizes mood, and norepinephrine, a stress hormone, and neurotransmitter.[5]
The Role of Cytokines: Chemical Messengers
Cytokines are proteins that play a role in cell signaling, which are released by the immune cells, during infection, reaching the brain by several routes.
According to a study conducted by Opp MR et al., “at least two cytokines, IL-1b (hereafter referred to as IL-1) and TNFa (hereafter referred to as TNF), is involved in the regulation of sleep.
These two cytokines may be considered sleep regulatory because data derived from electrophysiological, biochemical, and molecular genetic studies demonstrate specific effects on sleep-wake behavior.
Furthermore, electrophysiological, biochemical, and molecular responses to alterations in the activities of these cytokine systems can be predicted based on known signaling pathways, which can be targeted for intervention by selective antagonists, inhibiting them from acting on receptors. [6]
Therefore, it is required to conduct further studies regarding the role of cytokines as mediators of infection-induced alterations in sleep.
The focus of the studies should be on interfering with cytokine expression during infection, including outcome parameters that indicate the severity of illness.
Furthermore, the impact of prior sleep history on the ability to respond to the infectious challenge should be determined.
In the same line, actigraphy was introduced for objective estimation of habitual sleep duration and sleep quality measures. It can be helpful for patients who are unable to complete a sleep log reliably.
The Nemuri Gene & Sleep
Following the same trend, Toda et al. conducted a study on adult fruitflies to identify sleep regulators.
In the study, he overexpressed 8000 different genes within the nervous system of adult fruit flies and observed their effect on sleep.
Later, a single gene termed Nemuri was found to be associated with the increased sleeping tendency. The word Nemuri is derived from the Japanese word for sleep.[7]
The expression of NEMURI or NUR is observed to be low until the subject is infected or is sleep-deprived and is constitutively produced outside the brain.
According to an article by Oikonomou G. et al., “Fruit flies and mice that sleep more after infection show higher survival, but this observation is complicated by the fact that increased sleep was induced by sleep deprivation prior to infection.” [8]
Hence the identification of the NUR provided a clear mechanistic link between increased sleep and increased survivability during an infection.
Less often appreciated is that this increased sleep requirement is actually caused by the release of signaling molecules by our own immune system and nervous system, not by infectious agents.
References:
- Krueger JM, Frank MG, Wisor JP, Roy S. Sleep function: Toward elucidating an enigma. Sleep Med Rev. 2016;28. doi:10.1016/j.smrv.2015.08.005
- Ursin R, Bjorvatn B, Holsten F. Sleep Duration, Subjective Sleep Need, and Sleep Habits of 40- to 45-Year-Olds in the Hordaland Health Study. Sleep. 2005;28(10). doi:10.1093/sleep/28.10.1260
- Deboer T. Sleep homeostasis and the circadian clock: Do the circadian pacemaker and the sleep homeostat influence each other’s functioning? Neurobiol Sleep Circadian Rhythm. 2018;5. doi:10.1016/j.nbscr.2018.02.003
- Institute of Medicine (US) Committee on Sleep Medicine and Research. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. (HR C, BM A, eds.). National Academies Press (US); 2006.
- HONDA Y, TAKAHASHI K, TAKAHASHI S, et al. Growth Hormone Secretion During Nocturnal Sleep in Normal Subjects 1. J Clin Endocrinol Metab. 1969;29(1). doi:10.1210/jcem-29-1-20
- Opp MR. Cytokines and sleep. Sleep Med Rev. 2005;9(5). doi:10.1016/j.smrv.2005.01.002
- Toda H, Williams JA, Gulledge M, Sehgal A. A sleep-inducing gene, nemuri, links sleep and immune function in Drosophila. Science (80-). 2019;363(6426). doi:10.1126/science.aat1650
- Oikonomou G, Prober DA. Linking immunity and sickness-induced sleep. Science (80- ). 2019;363(6426). doi:10.1126/science.aaw2113 here we are talking about the depth of the sleep or decreased brain activity during the sleep so the term we can use is ‘DEEP’ sleep.
