Philadelphia, PA – A research team at the Perelman School of Medicine, University of Pennsylvania, has isolated a molecular player in the process of sleep homeostasis, at least in nematode roundworms.
The study, published in Current Biology, demonstrates even a slight lack of sleep in worms (Caenorhabditis elegans) is stressful.
Sleep homeostasis denotes a basic principle of sleep regulation. Homeostasis refers to regulatory mechanisms which are essential in maintaining the constancy of the physiology of organisms. Most organisms require some type of sleep or resting state in order to maintain a healthy homeostasis.
A homeostatic response in the body regulates sleep intensity, while the circadian clock regulates the timing of sleep within a 24 hour period.
A circadian clock is a biochemical mechanism which coordinates with a day-night cycle, managing circadian rhythms associated with sleep.
When you go too long without proper sleep — 6 to 8 uninterrupted hours every 24 hours equates to quality sleep — the deficit elicits a compensatory increase (homeostatic response) in the intensity and duration of sleep once attained. In contrast, excessive slumber reduces the propensity.
Essentially if you habitually stay up late often enough, your body will make every effort to recoup the loss, resulting in prolonged but less satisfying periods of rest until the body feels the deficit has been resolved.
To study the biological occurrences associated with sleep homeostasis David Raizen, MD, PhD, DABSM, assistant professor of Neurology, and his colleagues forced nematode roundworms to remain awake during a developmental stage when they normally sleep, called lethargus.
The sleep-deprived worms, as well as the researchers who too remained awake for the duration of the experiment, exhibited signs of sleep homeostasis. When they dozed off they were harder to wake up compared to the control group of worms.
Molecularly, the loss of sleep was associated with the migration of the stress-related DNA-binding protein DAF-16 (FOXO) from the cell cytoplasm into the nucleus. The protein activates expression of stress-related genes.
Raizen theorized the movement of DAF-16 from the cytoplasm to the nucleus of the cell was not just a consequence of sleep deprivation, but a biological trigger stimulating the homeostatic response to make up the deficit.
Knocking out the DAF-16 gene eliminated the animals’ homeostatic response to make up for lost rest. Unfortunately, most of the worms who’s DAF-16 genes were mutated (knocked out) died.
The team found if DAF-16 activity was reestablished in those with mutations sleep homeostasis was restored. However this was not deployed in neurons but in muscle tissue, suggesting an extra-neuronal component to sleep.
Whether DAF-16 (FOXO) will play the same role in humans is an open and intriguing question. Either way, the nematode worm model will be a useful basis in future related studies.
Sleep homeostasis is critical to human health. Both acute and chronic deprivation in humans has been linked to fatigue, weight gain, insulin resistance, and inhibited mobility and cognitive functions. In laboratory rats, a prolonged lack of sleep has caused death.
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