Deep sleep

Thanks to electroencephalogram records it was possible, at the beginning of the 21st century, to define the three major stages of behaviour in humans: wake, Rapid Eye Movement (REM) sleep, and Non-REM (NREM) sleep. REM and NREM sleep occur in cycles of 90 minutes thought a night and NREM is subdivided in three stages that together with REM constitute the “sleep architecture” (Sehgal and Mignot, 2011).

Slow-wave sleep (SWS) or deep sleep is predominant during the early part of sleep and its intensity and duration diminishes across the sleep period, whereas REM sleep becomes more intense and extensive towards the end of the sleep period. SWS is characterized by slow and high-amplitude of the encephalogram waves (delta waves), whereas in REM sleep the waves are faster and show a low-amplitude (Rasch and Born, 2013).

Studies performed in the 1930s in monozygotic twins firstly reported the influence of genetics on sleep. In 1992, Medori et al. described the first mutation in the PRNP gene linked to familial insomnia. Since then, many genetic variants have been related to sleep (Zhang and Fu, 2020).

Adenosine is a substance that is produced in the brain from the breakdown of the ATP molecule and which generates the need for sleep. When adenosine is accumulated, together with other substances, reduces the brain activity in some areas related to awake promoting sleep (Deboer, 2018).

The adenosine deaminase (ADA) gene encodes for an enzyme involved in the metabolism of adenosine. It appears that the ADA enzyme may be involved in homeostatic sleep-wake regulation and is expressed in sleep regulatory brain areas. In addition, it has been observed that adenosine levels vary along diurnal period (Rétey et al., 2005).

The functional variant rs73598374 (c.22G>A or D8N) in codon 8 of the ADA gene reduces the activity of the ADA enzyme by 20-30%.  The decrease in enzyme activity appears to lead to an increase in adenosine levels, which promotes SWS or deep sleep (Bachmann et al., 2012; Rétey et al., 2005; Mazzotti et al., 2012). D8N polymorphism has been associated with the duration of SWS and slow wave activity. Individuals with the CT and TT genotypes have higher sleep efficiency, longer duration of SWS and intensity of delta activity and fewer nocturnal awakenings (Mazzotti et al., 2012).

In complex living organisms, the internal clock that modulates the activity phase during the day sunlight, and the night is finely regulated. Sleep is defined as a natural reversible state of unconsciousness and decreased responsiveness to external stimuli with relatively low activity.

It is accepted the hypothesis that the timing of sleep in humans is regulated by two processes:

1) Homeostatic Process S: increased during wakefulness and dissipates during sleep. It is reflected in the duration and quality of sleep.

2) Process C: controlled by the circadian pacemaker which is encompassed with Earth day-night cycles thanks to the melatonin secretion. It restricts sleep to a determined time of the day.

Rest-behavior maintenance is essential for the growth and the nervous system. Sleep loss affects human behavior in a different manner and some persons are more vulnerable to sleep loss than others. Many researches have been conducted to properly understand genetic influences in sleep parameters variability among individuals and the underlying biological mechanisms in sleep associated disorders.

Sleep duration is a regulated process, when sleep is lost there are mechanisms that compensate it by extending subsequent sleep. Another sleep characteristic is sleep depth or sleep intensity, which varies according to the previous waking period duration. Deep sleep is the phase of sleep when the electrical activity delta waves on the brain show a slow frequency, and as much slow are the waves activity deeper is the sleep.

Deep sleep, often referred to as slow-wave sleep (SWS), is fundamental for memory consolidation and involves the incorporation of acquired hippocampal memories into the neocortex brain network for long-term storage.

Here is evaluated a genetic marker located in the ADA gene which encodes for an enzyme involved in adenosine production, a substance that it is accumulated during awake and regulates sleep pressure (need of sleep) and sleep depth.