Sufficient and restful nocturnal sleep is absolutely important for us, humans. Sleep researchers have been investigating for decades why and how our brain regenerates during sleep, but this remains a “scientific enigma” that is becoming increasingly clear. While asleep, we do not eat, drink, or reproduce and are vulnerable to predators, due to reduced responsiveness to environmental stimuli. Whatever function(s) sleep may have, there must be an evolutionary advantage to explain why we spent one third of our lives sleeping.

Sleep physiology:

The nocturnal sleep consists of alternating sleep phases, which can be represented by EEG waves, whereby deep sleep differs from lighter sleep. Normal sleep is divided into stages, as following:

  • non–rapid eye movement (NREM):
  1. NREM 1
  2. NREM 2
  3. NREM 3
  • rapid eye movement (REM) sleep

When we fall asleep, we enter non-REM sleep; as NREM stages progress, stronger stimuli are required to result in an awakening. REM sleep is the deepest stage, characterized by decreased EEG amplitude, muscle atonia, autonomic variability, and episodic rapid eye movement. After a variable period of time in REM sleep, we go back to a lighter stage. One journey through all stages is called a sleep cycle. During a normal 8-hour sleep period, we experience about 4-5 sleep cycles.

Sleep in adults: Stage N1 is considered a transition between wake and sleep. It occurs upon falling asleep and during brief arousal periods within sleep and usually accounts for 2–5% of total sleep time. Stage N2 occurs throughout the sleep period and represents 45–55% of total sleep time. Stage N3 (slow-wave sleep) occurs mostly in the first third of the night and constitutes 10–20% of total sleep time. REM represents 20–25% of total sleep time.

Sleep in elderly: In general, deep sleep (slow wave sleep) decreases with age. During nocturnal sleep, the proportion of NREM stage 1 and stage 2 increases with age, while the proportion of NREM 3 and REM sleep decreases. Latency to fall asleep and the number and duration of overnight arousal periods increase. Such sleep fragmentation and the disruption of deep sleep contribute to age-related cognitive decline and memory decline. It can be a worsening factor in patients with dementia.

Sleep functions:

Although the reason why we sleep is not totally elucidate, we have already enough evidence to prove how important it is to the human health. During sleep muscles growth, tissues are repaired and protein synthesis occur. Reproductive functions in both male and female are improved in those who sleep well. Our immune system is also influenced by sleep once it improves the action of natural killers (NK) cells, showing an important role in fighting cancer. Even some genes can be activated and inactivated by a good night of sleep.

Sleep functions in the brain:

1.) Information consolidation – learning 

Storing new knowledge in the long-term memory takes place mainly in hippocampus during REM sleep stage. Therefore, it is absolutely essential that all sleep phases are completed with sufficient duration and quality. During nocturnal sleep your brain is replaying and processing the events of your day and “presses the save button” to reinforce learning and memory, storing them in a “saved fold” and leaving space free for new information to added on the next day. So, a good night of sleep restores and enhances your memory and learning ability.

2.) Brain wash – the glymphatic system

The mechanisms underlying solute clearance from the brain’s extracellular space have puzzled neurologists for centuries, once the central nervous system (CNS) is the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent studies have led to the discovery of the glymphatic system, a glial-dependent perivascular network with a lymphatic-like function in the brain.

The glymphatic system is a macroscopic waste clearance system that utilizes a unique system of perivascular channels, formed by astroglial cells, to promote efficient elimination of soluble proteins and metabolites from the central nervous system. Besides waste elimination, the glymphatic system may also help distribute non-waste compounds, such as glucose, lipids, amino acids, and neurotransmitters related to volume transmission, in the brain. Intriguingly, the glymphatic system works mainly during sleep and is largely disengaged during wakefulness. The biological need for sleep across all species may therefore reflect that the brain must enter a specific state of activity that enables elimination of potentially neurotoxic waste products, including β-amyloid. 

The glymphatic pathway is a highly-organized fluid transport system where cerebrospinal fluid (CSF) and interstitial fluid (ISF) continuously interchange. In its initial segments, CSF from the subarachnoid space flows into the brain through perivascular spaces of the large arteries and is driven into the brain parenchyma through the perivascular spaces of penetrating arteries, also known as Virchow-Robins spaces. This flow across the brain parenchyma is facilitated from the water channels aquaporin 4 (AQP4) which is densely expressed by glial cells. While flowing, the CSF mixes with the ISF. In the interstitium, the mixed fluid disperses via a polarized net fluid movement directed towards the venous perivascular space (fig1).

Potential factors affecting glymphatic pathways include respiratory cycle, arterial pulsations, changes in vasomotor tone, postural changes and sleep. This last factor is significantly important in cleaning waste product: the clearance of amyloid beta (Aß) during sleep is twice as fast as during awake periods.

3.) Neuroplasticity 

Sleep regulates the strength of the communication between specific nerve cells and therefore influences synaptic plasticity, i.e., the ability of the brain to create new synapsis. REM sleep seems to affect the process of synapse formation and the maintenance of circuits. During sleep new pathways can be create to improve learning ability. 

Factors influencing REM sleep

Some drugs and also alcohol cause changes in sleep phases and fewer phases of REM sleep, which also causes a deterioration of regeneration and re-formation of nerve cells. Sleep apnea is also a problem that affects the quality and quantity of sleep and should be considered.

How much sleep do we need?

The opinions on this topic differ and lie between 7 and 10 hours per night. It is important to bear in mind that we are individuals and that the required sleeping time certainly varies from person to person. But if you feel as if you are wheeled out in the morning and not recovered, then either your sleep duration or the sleep quality is not right for you.

Things or activities turn night into day

  • Bright light, especially artificial light with a high blue component (screens, smartphones, tablets, cheap LEDs, certain fluorescent tubes)
  • Television
  • Night work
  • Not able to “switch off”

References

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  7. Rasmussen MK, Mestre H, Nedergaard M. The glymphatic pathway in neurological disorders. Lancet Neurol. 2018;17(11):1016–1024. doi:10.1016/S1474-4422(18)30318-1 https://pubmed.ncbi.nlm.nih.gov/28466758/
  8. Jessen NA, Munk AS, Lundgaard I, Nedergaard M. The Glymphatic System: A Beginner’s Guide. Neurochem Res. 2015;40(12):2583–2599. doi:10.1007/s11064-015-1581-6 https://pubmed.ncbi.nlm.nih.gov/30480554/
  9. Plog BA, Nedergaard M. The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future. Annu Rev Pathol. 2018;13:379–394. doi:10.1146/annurev-pathol-051217-111018 https://pubmed.ncbi.nlm.nih.gov/29195051/
  10. Yulug B, Hanoglu L, Kilic E. Does sleep disturbance affect the amyloid clearance mechanisms in Alzheimer’s disease?. Psychiatry Clin Neurosci. 2017;71(10):673–677. doi:10.1111/pcn.12539 https://pubmed.ncbi.nlm.nih.gov/29632177/
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