A cellular mechanism discovered by Bar-Ilan University researchers may provide the key to solving this age-old mystery * PARP1 is an "antenna" that signals that it is time to sleep
Why do humans spend a third of their lives sleeping? Why do animals sleep? Throughout evolution, sleep has remained universal and essential for all organisms with a nervous system, including invertebrates such as flies, worms and even jellyfish. Why do animals sleep despite the constant threat from predators, and how does sleep benefit the brain and individual cells? These questions are still a mystery.
In a new study published in the journal Molecular Cell, researchers at Bar Ilan University in Israel took another step toward solving the mystery when they discovered a sleep mechanism in zebrafish and supporting evidence in mice.
The research was conducted under the leadership of Prof. Lior Appelbaum from the Goodman Faculty of Life Sciences at Bar Ilan University and the Multidisciplinary Center for Brain Research named after Gonda (Goldschmidt) together with postdoctoral student David Zeda.
When we are awake homeostatic sleep pressure builds up in the body. This pressure increases as we stay awake and decreases during sleep to a low after a full and good night's sleep.
What causes the homeostatic pressure to increase to the point where we feel the need to sleep, and what happens at night that reduces the pressure to such an extent that we are ready to start a new day? During waking hours, DNA damage accumulates in the nerve cells. These damages are caused by various reasons, including ultraviolet light, nerve cell activity, radiation, oxidative stress and enzymatic errors. During sleep and waking hours, repair systems in each cell repair the breaks in the DNA. However, the DNA damage in the nerve cells continues to accumulate while awake, and too much damage in the brain may reach dangerous levels that must be reduced. Research shows that sleep mobilizes DNA repair systems and promotes efficient repair that allows a new day to begin.
In a series of experiments, the researchers sought to determine if the accumulation of DNA damage is the cause of homeostatic stress and the subsequent sleep state. Using radiation, pharmacology and optogenetics, they caused DNA damage in zebrafish to examine how this affects their sleep. Thanks to their complete transparency, nocturnal sleep and a simple brain similar to that of humans, zebrafish are the perfect organism to study this phenomenon.
As the DNA damage increased, so did the need for sleep. The experiment showed that at a certain point the accumulation of DNA damage reached a maximum threshold and increased the sleep pressure (the homeostatic pressure) to such an extent that the need to sleep arose in the fish and the fish fell asleep. The sleep helped to repair the DNA and reduce the damage.
How many hours of sleep are enough?
There's nothing like a good night's sleep. After verifying that the accumulation of DNA damage is the driving force behind the sleep process, the researchers wanted to know if it was possible to determine the minimum sleep time needed for zebrafish to reduce sleep stress and DNA damage. Since zebrafish, like humans, are sensitive to light disturbances, the dark period gradually shortens during the night. After measuring DNA damage and sleep, it was determined that six hours of sleep a night is enough to reduce DNA damage. Surprisingly, after less than six hours of sleep, the DNA damage did not decrease sufficiently, and the zebrafish continued to sleep even in daylight.
PARP1 He is an "antenna" that signals that it is time to sleep
What mechanism in the brain tells us that we need to sleep to encourage efficient DNA repair? The PARP1 protein, which is part of the DNA damage repair system, is one of the first responders. PARP1 marks the DNA damage sites in the cells and mobilizes the relevant systems to clean up the DNA damage. Depending on the DNA damage, PARP1 accumulation at DNA breakage sites increases during wakefulness and decreases during sleep. Through genetic and pharmacological manipulation, overexpression and knockdown of PARP1 revealed that not only does increasing PARP1 promote sleep, but it also increases sleep-dependent repair. On the other hand, suppression of PARP1 blocked the signaling to repair DNA damage. The result was that the fish did not know they were tired, did not fall asleep, and no DNA damage was repaired.
To strengthen the findings from the zebrafish, the role of PARP1 in regulating sleep was also tested in mice using an electroencephalogram (EEG) in collaboration with Professor Yuval Nir from Tel Aviv University. As in zebrafish, inhibition of PARP1 protein activity reduced the duration and quality of non-rapid eye movement (NREM) sleep. "PARP1 pathways are able to signal to the brain that it must sleep to carry out DNA repair," says Prof. Applebraum.
In a previous study, Professor Appelbaum and his team used 1D time-lapse imaging to determine that sleep increases chromosomal dynamics. Now another piece has been added to the package, PARPXNUMX which increases sleep and chromosomal dynamics and promotes the repair of DNA damage accumulated during waking hours. It is possible that the DNA maintenance process in the nerve cells while awake is not efficient enough and therefore a period of sleep with reduced input to the brain is required.
These latest findings provide a detailed description of the "chain of events" that explains sleep at the single cell level. This mechanism may explain the connection between sleep disorders, old age and degenerative neurological disorders such as Parkinson's or Alzheimer's. Professor Appelbaum believes that future research will help to apply this sleep function to other animals from lower invertebrates to, eventually, humans.
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One response
Questionable title
"How do we know we are tired"?????
tired = know you are tired