To sleep, perchance to let DNA be repaired: Study finds new reason for slumber
Bar-Ilan University researchers show that individual neurons need sleep to give chromosomal repair system a chance to clear out daily debris accumulated during wake time
Shoshanna Solomon was The Times of Israel's Startups and Business reporter
Humans spend one third of their lives sleeping, and most other animals — such as flies, worms, fish, dogs and jellyfish — sleep as well. But even as we realize that sleep is an important part of our lives, why we sleep still remains something of a mystery.
To sleep “doesn’t make sense in terms of survival,” said Prof. Lior Appelbaum of Bar-Ilan University’s Mina and Everard Goodman Faculty of Life Sciences and Gonda (Goldschmied) Multidisciplinary Brain Research Center. Sleeping organisms can be attacked by predators, so it would be better to avoid it, he said. And yet, sleep is required.
The subject of sleep has been studied for years, and it has been determined that sleep is important for brain performance overall.
Appelbaum, however, set out with a team of researchers to study the impact of sleep on the neuron, or nerve cell, which is the fundamental unit of the brain and the nervous system.
The researchers said their findings show, for the first time ever, that single neurons need sleep. And the reason for that is so that the daily debris accumulated in their DNA, long molecules packaged into structures called chromosomes, can be cleaned out. Nerve cells sleep, the researchers said, so that chromosomes can do daily “nuclear maintenance.”
“It’s like potholes in the road,” Appelbaum said in a statement released by the university. “Roads accumulate wear and tear, especially during daytime rush hours, and it is most convenient and efficient to fix them at night, when there is light traffic.”
The researchers say this new explanation of the role of sleep could explain how sleep and sleep disturbances affect brain performance, aging and various brain disorders. The study was published on Tuesday in the journal Nature Communications.
In their work, the researchers, led by Appelbaum, used 3D time-lapse imaging techniques in live baby zebrafish, which are transparent at that age, enabling them to more easily track the DNA inside the neurons and follow the activity of chromosomes during the day and at night.
Because their brains have similarities to those of humans, zebrafish are a good model for the study of single cells. Using a high-resolution microscope, the movement of DNA and nuclear proteins within the cell was observed while the fish were awake and asleep.
As our bodies undergo regular neuronal activity or radiation or oxidative stress, our DNA gets damaged, or, as Appelbaum said, the accumulation of DNA damage is the “price of wakefulness.”
DNA repair systems within each cell correct this damage. However, the researchers found while studying zebrafish, during wakeful hours the chromosomes in charge of correcting this damage didn’t work very hard, allowing DNA damage to accumulate and even reach unsafe levels.
These same chromosomes, however, became active when the body rested. During sleep, like on a road with less traffic, the chromosomes get into a cleaning frenzy and set out normalize the levels of DNA damage in each neuron.
“The activity of chromosomes increases at night,” Appelbaum explained by phone. “The role of sleep is to increase the chromosome dynamics to reduce DNA damage.”
If a fish was deprived of sleep for several hours the DNA damage increased even more, he said.
“So why do we sleep? Or why do zebrafish sleep?” Appelbaum asked. Because DNA damage in neurons becomes “risky at a specific threshold — if you accumulate more and more damage at the end it is very dangerous and the neuron can die.”
So, humans and animals “have to sleep to enter this offline mode” when the cell is not active, constantly bombarded with new input. When the neurons sleep, the chromosomes have the “time to do this nuclear maintenance, to clean up everything and clear out all this damage and so the neuron will be ready for the following day.”
“When the organism enters the offline world — it comes back to what it was at the beginning of the day. It goes back to baseline condition,” he said.
The study is important, he said because it shows “one more reason” for why organisms sleep, “which is a fundamental biological question. We sleep to increase chromosome movement and allow efficient repair during the night.”
This may help understand why sleep deprivation will eventually affect brain health and cause various neurodegenerative diseases, he said — “because DNA damage is accumulated.”
The team of researchers was led by Appelbaum and included his doctoral student David Zada, first author of the study, as well as co-authors Dr. Tali Lerer-Goldshtein, Dr. Irina Bronshtein, and Prof. Yuval Garini.
