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Regeneration during sleep

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Being unconscious and defenseless for hours at a time poses a risk for every living creature. What makes sleep so important that it is worth taking the risk?

Dr. Klaus Duffner | Germany

Bats, cats, chickens, elephants, horses, fruit flies and, of course, human beings – we all need our sleep. And it has to be the right kind of sleep. Just why humans and animals sleep has still not been fully explained, and it is one of the greatest unsolved puzzles in science today. It is highly risky for all creatures to spend several hours unconscious in the natural world. Despite this, sleep is so important that this is an acceptable risk. One thing is certain: anyone who skips his or her nightly rest too long, dies. Moreover, chronic sleep deprivation, or chronic sleep disorders, constitute an added risk factor for a number of conditions, such as influenza, epilepsy, Alzheimer’s disease, obesity or stroke. Sleep is thus very important.


An energy boost to the brain

Anyone who, after having fallen into bed the night before completely exhausted, limp as a rag and with a head filled with befuddled thoughts, awakes in the morning fully refreshed can scarcely understand all that sleep has done for him. A new day begins afresh, full of energy and ideas. How is this “fountain of youth” to be explained? A currently well-regarded theory about the function of sleep proposes that it allows the brain to refill its reserves of energy. In fact, researchers working with Radhika Basheer and Markus Dworak at Harvard Medical School in Boston have been able to establish that mice gain a powerful energy boost in the early phase of their sleep.1

What is striking is that it is principally restricted to those areas of the brain which are only active in the waking state. The level of ATP (adenosine triphosphate) molecules increases significantly in these areas. ATP is the body’s energy currency and is indispensable for most of its metabolic processes. On the other hand, when mice were kept awake during the period when they were normally asleep, then no increase in ATP occurred. But as soon as the creatures nodded off, the ATP boost switched back on again. It could thus be concluded that the supply is influenced by the time of day, or by an “inner clock.”

The question remains: why is it that such a supply of energy does not also occur in the waking state? The researchers have an explanation: during the waking phase the brain is constantly engaged in energy-intensive nerve activity, and it is careful to ensure the availability of adequate, uniform levels of energy. It is only through a particular signal, such as falling asleep, that this condition can be overcome. For the first time just a few years ago, researchers in the USA were able to measure how much less energy is consumed during sleep than in the waking state.2 A medium-sized body saves approximately 134 kilocalories or 562 kilojoules by sleeping, in comparison with lying awake. This may only correspond to the energy value of two slices of bread, but nevertheless, the reduction in energy consumption may be the start signal for refilling ATP reserves, for producing certain biomolecules such as proteins or fatty acids, and thus for regenerating the body. 

Night-time cleaning service

Alongside the “energy question,” in the last few years scientists have added a further remarkable aspect to another potential physiological function of sleep. According to the results of a study conducted by Lulu Xie and her team at the University of Rochester, New York, harmful metabolites are cleared out of the brain during sleep.3 The brain has only a limited amount of energy available, which is used for mental functions during the day. So that these functions are not negatively impacted, it reschedules its main cleaning regime to the after-hours. The brain must decide between two functional states, says co-author Maiken Nedergaard in the journal Science, “either it is awake and on the alert, or it’s asleep and can have a bit of a tidy up.”

The so-called glymphatic system, which was only discovered a few years ago, is particularly important for these nocturnal cleaning activities. It is a network of tiny channels that transport cerebral fluid, and in the cranium it replaces the lymph system, which is responsible for carrying waste products away in the rest of our body. These tiny drainage channels are not controlled by nerve cells but by glial cells, which carry out the actual protective and enveloping functions in the brain.

Gaps to allow drainage

In order to gain more knowledge about this drainage system, scientists injected a colored dye into the cerebral fluid of sleeping mice. They were able to establish that it penetrated much more deeply into the tissue during sleep than in the waking state. While the dye penetrated approximately ten-times more effectively into the depths of the drainage system in sleeping animals, it was restricted to the surface of the brain in mice that were awake. At the same time, the researchers showed that the nerve cells contract during sleep, creating gaps. The intercellular space in the brains of rodents that were awake accounted for only 14 percent of the cerebral volume, while in sleeping animals it was 23 percent. Unusable proteins and other substances can drain away through these nocturnally-formed gaps, along with the cerebral fluid, into the bloodstream. These include β-amyloids that are associated with Alzheimer’s disease, for example. They were cleared away during sleep twice as quickly as during the waking state. The neurotransmitter noradrenalin may well play an important role in these contraction processes, say the researchers, as its concentration is reduced in the sleeping brain.

The body needs an adequate amount of sleep in order to carry out this “cleaning service” efficiently. The American researchers suggest that if this is interfered with for any length of time, then substances hazardous to health can accumulate in the brain and create favorable conditions for diseases such as Alzheimer’s or Parkinson’s disease.

Whether it is the replenishment of our energy reserves or the removal of harmful substances that is responsible for our need to sleep - a small miracle of regeneration takes place in our bodies every night.

Dr. Klaus Duffner

Dr. Klaus Duffner | Germany

Scientific Journalist
Medizin & Wissen Freiburg

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