DNA Damage Makes Zebrafish Sleepy

Very recommendable! More evidence how important sleep is for our health! This research suggests that in the near future humans might be able to reduce their need for sleep by using more effective DNA damage repair.

"... By labeling repair proteins in live zebrafish larvae with florescent markers and using real-time imaging, the researchers found that during sleep, the repair proteins are recruited to DNA damage sites in the neurons of the dorsal pallium, the zebrafish equivalent of the brain’s neocortex. “Sleep increased the clustering of repair proteins to the DNA damage and the induced repair became more efficient” than during wakefulness, Appelbaum says. ... 

Parp1 detects DNA damage and recruits repair proteins to mend the breaks ... it might act as a sensor to trigger sleep. Indeed, the researchers observed that Parp1 clustering on chromatin in the brain increases during the day and reduces to baseline level by the end of the night. When they increased levels of Parp1 in zebrafish larvae, the larvae slept longer, but when Parp1 was inhibited, the larvae slept for a shorter period of time—though they caught up on lost sleep once the inhibitor was withdrawn. In the larvae treated with the Parp1 inhibitor, more DNA damage accumulated both during the day and the night than in larvae where Parp1 functioned normally. After the drug was withdrawn in the treated embryos and they caught up on sleep, DNA damage returned to normal levels, indicating that Parp1 reduces DNA damage in neurons and that even when DNA is intensely damaged, and larvae without functioning Parp1 don’t sense the need to sleep. ...
The researchers also found that inhibiting Parp1 reduces the length of non-REM sleep in adult mice, indicating that the same mechanism likely connects DNA damage, Parp1, and sleep in these mammals. ...
“They showed that fish sleep is important for DNA repair, [and] they confirm their findings in mouse and showed that Parp1 induced non-REM sleep,” ... adding that the mouse results indicate this mechanism must be present in humans as well. ..."

From the abstract:

"... In flies, zebrafish, mice, and humans, DNA damage levels increase during wakefulness and decrease during sleep. Here, we show that 6h of consolidated sleep is sufficient to reduce DNA damage in the zebrafish dorsal pallium. Induction of DNA damage by neuronal activity and mutagens triggered sleep and DNA repair. The activity of the DNA damage response (DDR) proteins Rad52 and Ku80 increased during sleep, and chromosome dynamics enhanced Rad52 activity. The activity of the DDR initiator poly(ADP-ribose) polymerase 1 (Parp1) increased following sleep deprivation. In both larva zebrafish and adult mice, Parp1 promoted sleep. Inhibition of Parp1 activity reduced sleep-dependent chromosome dynamics and repair. These results demonstrate that DNA damage is a homeostatic driver for sleep, and Parp1 pathways can sense this cellular pressure and facilitate sleep and repair activity."

DNA Damage Makes Zebrafish Sleepy | The Scientist Magazine® Buildup of a DNA-repair protein in brain cells spurs shut-eye in the fish, a study finds, and similar results in mice suggest the mechanism is widespread in animals.

Parp1 promotes sleep, which enhances DNA repair in neurons (no public access)