Animals are similar in a lot of ways. Ways of nutrition, respiration, metabolism and to some extent, even behaviour. But, of all these similarities, there is one particular feature common to all of us, that is, SLEEP! Yes, sleeping is a common and vital behavioural adaptation that is shown by all vertebrate animals, irrespective of their level of complexity or organisation. But, why do we actually need to sleep? I mean, except for the fact that you don’t want those dark circles creating a perimeter around your eye balls, what is the actual biological significance of sleep!
Abstract:
In this article, we will broadly discuss about the significance of sleep in vertebrate animals and the prime molecule associated with its induction. While sleep is necessary for various physical reasons and to overcome stress responses of the body, it is even more crucial for the various biochemical processes occurring. The prime process that will be discussed here is DNA damage repair. Previous researches by neuroscientist Lior Appelbaum and his team at Bar-Ilan University in Israel had found that DNA damage increases during the day and decreases during the night, suggesting that sleep could help repair this damage. In a recent study, they investigated whether DNA damage is the reason why zebrafish and other related vertebrate animals sleep. When postdoc David Zada and other authors induced DNA damage in the neurons of zebrafish larvae by inducing neuronal activity or using UV radiation, the fish slept longer since they got tired. Further findings suggested the involvement of Parp1 protein, which detects DNA damage and triggers sleep in zebrafish.
Introduction:
Cells routinely face various levels of stress such as exposure to radiations, increased level of reactive oxidative species, accumulation of waste products and so on. While some of these can be overcome by simple biochemical alterations, others lead to more serious side effects in the form of DNA damage. The DNA damage is further subjected to repairing processes, wherein it undergoes series of molecular pathways to be rectified. However, in case of irreparable DNA damages, the cell is signalled to undergo apoptosis or programmed cell death.
In today’s era of modern science, model specimens play an important role in order to study the biological pathology and its related aspects. One such model of great significance is zebrafish. But why zebrafish? The answer lies in the animals’ looks and physiology. Zebrafish has an almost transparent body form, which allows the researchers to observe its developmental stages on induction of various chemicals, without actually sacrificing the animal.
By using florescent markers, damage repair proteins were labelled in live zebrafish larvae. Further, 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 (which is the zebrafish equivalent of the brain’s neocortex). The scientists interpreted that “Sleep increased the clustering of repair proteins to the DNA damage and the induced repair became more efficient than during wakefulness.”
Damage induced sleep: “Role of Parp1 protein”
The prime interest of the scientists was to understand the correlation between DNA damage and sleep. It has already been found that the Parp1 has major significance in detecting DNA damage and recruiting repair proteins to mend these breaks. This damage sensor protein was observed to cluster on chromatin in the brain, dominantly more in the day time and reduces to baseline level by the end of the night. Experimentally, on increasing the levels of Parp1 in zebrafish larvae, induced the larvae to sleep for longer period of time as compared to when the protein was inhibited. However, the larvae caught up on lost sleep once the inhibitor was withdrawn.
This further led to observations of elevated DNA damage in case of Parp1 inhibited larvae, as compared to the larvae with normal functioning Parp1 protein. This indicated that Parp1 reduces DNA damage in neurons by inducing sleep. However, non functioning Parp1 leads to absence in sensing the need to sleep, even in cases of intense DNA damage.
These data suggest that DNA damage and the urge to sleep is all related to the specific threshold of Parp1. Sleep plays a vital role in efficiently repairing the damages. As soon as the Parp1 reaches its threshold, it drives the phenomenon of sleep. In our day to day life, the cell is exposed to lots of stress, leading to proportional increase in DNA damage. If untreated, these damages will start degenerating the cell.
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.
It was showed that fish sleep is important for DNA repair and was even further confirmed in mouse. The mammal showed that Parp1 induces non-REM (Rapid eye movement) sleep, thus indicating that a similar mechanism must be present in humans as well. Particularly as neurons are not replaced during our lives, DNA damage repair during sleep may be a mechanism to protect neuronal health. “Neurons need a tight maintenance program, and it seems that sleep is part of it. Sleep is critical to repair the damage that is generated during wakefulness.” In future research, Appelbaum says he hopes to find out whether and how these insights into sleep and DNA damage bear on neurodegenerative diseases, which can be accompanied by sleep disturbances.
Conclusion:
The research concluded so far reveals the effective mechanism behind sleep. It also establishes the strong connection between DNA damage and sleep periods. As in the case of zebrafish, Parp1 was evidently found to bridge DNA damage and sleep, so was recorded in the case of mouse. Hence, the application of this research regarding Parp1 can be extended to other mammals, including humans. Further, this information can be utilised in case of human related neuro-degenerative diseases where sleep induced repair is the only method for mainting the population of functioning neurons. This importance arises because of the inability of neurons to regenerate in mammals.