Thursday, December 2

Why do we sleep? The discovery of a biological mechanism sheds light on this ancient mystery


We sleep to rest, but such a simple answer tells us nothing about what it means to get tired and what regularly forces us – us and the animals – to disconnect for a few hours. Although its benefits have been studied, sleep is one of the great enigmas of nature. Now, an Israeli team has managed to unravel the brain mechanism that explains why we spend a third of our lives in that other reality, that of dreams.

In a new study, published in the magazine Molecular Cell, researchers from Israel’s Bar-Ilan University have taken a step forward in solving this mystery. Throughout evolution, sleep has remained universal and essential to all organisms with a nervous system, including invertebrates such as flies, worms, and even jellyfish. So there must be a powerful reason why evolution has preserved the healthy habit of sleeping.

Researchers, according to the University itself in a statement, have discovered the sleep mechanism in zebrafish, and have also performed some supporting tests in mice. It was about answering the question of why animals sleep, despite the continuous threat of predators.

There must therefore be a powerful reason why evolution has preserved the healthy habit of sleeping.

There are abundant studies of how sleep benefits the brain and cells. By the end of october, Magazine Science published a special issue where he reviewed the importance of sleep to fix memories and to ensure the proper functioning of the body during wakefulness (cognitive abilities, reflexes, etc.).

Other studies focus on the ‘maintenance’ functions that the brain performs during sleep, such as the elimination of ‘metabolites’, remnants of the body’s metabolic functions. Something similar to the garbage trucks that clean the city at night. The research released today sheds new light on this latest nocturnal brain activity.

The fatigue

When we are awake the homeostatic pressure from sleep (what we commonly call tiredness) builds up in the body. This pressure increases the longer we stay awake and decreases when we sleep, reaching a minimum after a full and restful night’s sleep. What is it that causes the homeostatic pressure to rise to a point where we feel like we should go to sleep? What is it that at night manages to reduce that homeostatic pressure to such an extent that we are ready to start a new day?

It is known that damage to the DNA of neurons accumulates during waking hours. This damage can be caused both by external elements – such as ultraviolet light and radiation – and by certain biological processes, such as neuronal activity itself, oxidative stress and enzymatic errors.

During sleep and wakefulness, repair systems within each cell correct DNA breaks. However, damage to the DNA of neurons continues to accumulate during wakefulness, and too much damage to the DNA of the brain can reach dangerous levels that need to be corrected.

As damage to the fish’s DNA increased, so did its need for sleep

In a series of experiments, researchers have tried to determine whether the accumulation of DNA damage could be the ‘motor’ that triggers the feeling of tiredness (the homeostatic pressure) and the subsequent state of sleep. Using radiation, drugs and optogenetic techniques (optical and genetic methods), they induced damage to the zebrafish’s DNA to examine how they affected their sleep. The zebrafish is a perfect organism to study this phenomenon. During much of their development the specimens are practically transparent. His brain is simple and his dream is similar to that of humans.

As damage to the fish’s DNA increased, so did its need for sleep. The experiment suggested that at some point the accumulation of DNA damage would reach a maximum threshold and increase the feeling of tiredness until the fish felt the need to sleep. Just what they did. The ensuing sleep facilitated DNA repair.

The study was led by Professor Lior Appelbaum, from Bar-Ilan’s Goodman College of Life Sciences and the Gonda Center for Multidisciplinary Brain Research (Goldschmied), together with postdoctoral researcher Dr. David Zada.

How many hours of sleep are enough?

There is nothing like a good night’s sleep. After verifying that accumulated DNA damage is the driving force behind the sleep process, the researchers were anxious – according to the University – to know if it is possible to determine the minimum time that zebrafish need to sleep in order to reduce feeling tired and DNA damage.

Since, like humans, zebrafish are sensitive to light interruption, the period of darkness at night was gradually decreased. It was finally determined that six hours of sleep each night is enough to reduce DNA damage. Surprisingly, after less than six hours of sleep, the DNA damage was not adequately reduced, and the zebrafish continued to sleep even during daylight.

Fish that do not feel tired

What is the brain mechanism that tells us we need sleep to facilitate effective DNA repair? The PARP1 protein, which is part of the DNA damage repair system, is one of the first to respond rapidly. PARP1 marks the sites in cells where DNA has been damaged and recruits all relevant systems for repair.

Depending on the damage, the accumulation of PARP1 in these places increases during wakefulness and decreases during sleep. Using experimental techniques, the scientists found not only that the increase in PARP1 promotes sleep, but also increases sleep-related repairs. In contrast, inhibition of PARP1 blocked the DNA damage repair signal. As a result, the fish were not fully aware that they were tired, did not fall asleep, and the necessary repair did not occur.

Inhibition of PARP1 blocked the DNA damage repair signal. As a result, the fish were not fully aware that they were tired.

To corroborate the findings in zebrafish, the role of PARP1 in sleep regulation was again tested in mice using EEG measurements. As with zebrafish, inhibiting PARP1 activity reduced the duration and quality of so-called ‘non-rapid eye movement sleep’, which is made up of the early stages of sleep, from drowsiness to deep sleep (the so-called REM phase).

“PARP1 pathways are able to signal to the brain that it needs sleep for DNA repair to occur,” says Professor Appelbaum.

Solve the puzzle

In a previous study, Professor Appelbaum and his team had used 3D images obtained at specified intervals to conclude that sleep increases chromosome dynamics. Now they add to the puzzle this new piece, the PARP1 protein, which increases sleep and chromosome dynamics, facilitating the efficient repair of DNA damage accumulated during wakefulness.

The conclusion of this study is that it is possible that the neuronal DNA maintenance process is not efficient enough during waking hours and that, therefore, for repair to occur, the brain needs a period of sleep ‘unplugged’ from the environment, with a reduced input of external stimuli.

These latest findings provide a detailed description of the “chain of events” that explain sleep at the single-cell level. This mechanism could also explain the relationship between sleep disorders, aging, and neurodegenerative disorders, such as Parkinson’s and Alzheimer’s.



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