The brain has a waste disposal system that is activated especially during sleep. We know this system by the name “the glymphatic system of the brain.” Almost all neurodegenerative pathologies are linked to an accumulation of cellular waste.
Eliminating waste is a vital activity to ensure the proper functioning of an organ. The brain, very active, is no exception. But because of the blood-brain barrier that protects it from large molecules that could attack it, it must be managed to get around it to get rid of proteins that could pile up.
Like all organs, the brain consumes energy and nutrients and produces more or less toxic residues from this metabolic activity. Therefore, during waking, the brain accumulates waste due to the activity of the neurons.
Researchers at the University of Rochester Medical Center – led by Maiken Nedergaard and Jeffrey Iliff – in a study published in the journal Science Translational Medicine in August 2012, then in July 2013 in Science, show that brain cells shrink during sleep to create spaces – the interstitial space – between the neurons and allow the fluid to “wash” the brain.
Until then, it was thought that brain cleansing was done exclusively by passive diffusion of cerebrospinal fluid from the cerebral ventricles, a very slow evacuation mechanism for an organ as active as the brain.
This new study proves that we need a certain amount of sleep every night because the brain uses this time to get rid of the toxic metabolic by-products that would otherwise accumulate and disrupt the functions of the brain. brain, destroying neurons and potentially causing neurodegenerative disorders.
The research team believes that this waste disposal system is one of the fundamental reasons for sleep. In particular, they suggest that a defect in this system, which would prevent the sweeping of certain toxic proteins, may play a role in brain disorders. This study suggests that the “household” may be one of the main reasons for the role of sleep.
Researchers used a recent technique, called 2-photon microscopy, to visualize in real-time the flow of blood and cerebrospinal fluid into the brain of a living animal.
This study completes knowledge about the brain, primarily about the actual physical and chemical reason for sleep, and the role of interstitial space. On the mechanism and conditions that lead to the loss of brain cells; as in the case of Alzheimer’s disease or Parkinson’s disease, which are characterized by the accumulation of damaged proteins in the brain.
It is surprising that such a fundamental system for proper brain function has so far been able to escape the sagacity of researchers. The main reason is that this glymphatic system only works in a living brain and only when it is intact: it was impossible to observe it on post-mortem brains and the visualization methods available did not allow until shortly to detect it in living subjects.
In the body, the lymphatic system is the system responsible for the disposal of cellular waste. A liquid called lymph bathes the cells and tissues of the body, collects cellular waste and discharges into the bloodstream to be filtered by the body. However, the lymphatic system does not understand the brain. It has its own internal ecosystem and is surrounded by the blood-brain barrier, which controls what goes in and out of the organ. These characteristics have long remained an enigma for scientists.
The glymphatic system of the brain consists of star-shaped glial cells called astrocytes, which form a network of water channels surrounding the blood vessels of the brain.
Glial cells that keep nerve cells alive, shrink during sleep. This increases the size of what is called “interstitial space”, the gaps between brain tissues, which allows more fluidity for the washing of toxins. Researchers indicate that this function is vital to stay alive and that it does not seem to be possible while the mind is awake. The team is unclear why space increases during sleep, but they theorize that brain cells are shrinking.
Cerebrospinal fluid (CSF) circulates in the brain along the canals that surround the arteries. Then the liquid “cleans” through the brain tissue and mixes with the interstitial fluid-filled with waste that surrounds the brain cells. Finally, CSF accumulates in the channels through the veins and is removed from the brain, taking with it the metabolic waste.
By pumping cerebrospinal fluid through the brain tissue, the glymphatic system removes waste from the brain and sends it back into the circulatory system of the body. From there, the waste reaches the liver, where it is eventually eliminated.
The brain has only limited energy available to it and it must choose between two different functional states, either awake and conscious or asleep and in the cleaning phase.
The researchers’ findings are based on the discovery of this specific brain network, which transports waste to the brain – a kind of brain drain.
According to the researchers the glymphatic system of the brain is not only faster, but it also allows to reach more remote areas of brain tissue. Given the intense metabolism of the brain and its extreme sensitivity, it is not surprising that its waste disposal mechanism is more specialized and extensive than previously thought.
2 – The Blood-Brain Barrier: A Complex Defense Device
The blood-brain barrier is an anatomical barrier that filters and controls the passage of blood substances and prevents them from freely passing from blood to cerebrospinal fluid.
It consists of a continuous vascular wall surrounded by astrocytic glial cell proli-cations that stow to form an additional envelope. These two walls, vascular and glial, exert a function of selection and ensure the sorting of the substances admitted into the cerebral parenchyma. Highly impervious, this barrier consists of contiguous cells welded to each other.
In the meninges, these barriers have very thin spaces that allow very small molecules to infiltrate. Usually, normal size proteins do not pass through these two barriers, except during inflammation, where these joins between cells expand.
However, even today is relatively little known about the blood-brain barrier. Since the discoveries of Lewandowsky and the bacteriologists Ehrlich and Goldmann during the first decade of the twentieth century, six more decades have elapsed until the exact location of the barrier was localized – in the endothelial capillary cells – thanks to the electron microscope.
3 – A New Pathway Against Neurodegenerative Diseases
Although their study focuses on mouse brains, the authors believe that an identical system exists in humans whose brain is very close to that of the small rodent, at least physiologically. This discovery could have important therapeutic applications, particularly in the treatment of neurodegenerative pathologies, such as Alzheimer’s or Parkinson’s diseases. Alzheimer’s disease and other neurodegenerative diseases are associated not only with the accumulation of its waste but also with a lack of sleep.
The researchers found that more than half of the aggregates of beta-amyloid – a protein that accumulates in the brains of patients with Alzheimer’s – are eliminated via the glymphatic system. If the glymphatic system of the brain is no longer able to clean the brain as it should, either because of aging or following a trauma, the waste will accumulate in the brain. Increasing the activity of the glymphatic system would probably prevent the accumulation of amyloid deposits, or even provide a way to liquidate aggregates accumulated when Alzheimer’s disease is already established.
4 – Beta-Amyloid Protein
These proteins accumulate in the case of Alzheimer’s disease and contribute to the death of neurons. In the phase of sleep, their elimination is twice as fast as during waking.
Researchers injected beta-amyloid into the brain of healthy mice and genetically modified mice to deactivate their glymphatic system. While normal mice are able to rapidly remove protein from their brain tissue, glymphatic system-free mice take much longer.
This could explain why many neurological disorders are associated with sleep disorders. A rest deficit could be directly involved, facilitating the accumulation of harmful proteins, such as beta-amyloid, but also alpha-synuclein, which is implicated in Parkinson’s disease.
Other questions challenge researchers. First, they think that brainwashing helps with recovery. But to what extent does the accumulation of metabolic residues affect the feeling of fatigue? On the other hand, how do glial cell channels change conformation during sleep? If the researchers seem to have described one of the functions of sleep, it could surely be that it is not the only one. The investigation is therefore far from over.
Thus, increasing the activity of the glymphatic system of the brain could help prevent amyloid deposits, conclude the authors who hope their findings will have implications for many neurological diseases, from Alzheimer’s or Parkinson’s to stroke.
5 – Sleeping Allows the Brain to Clean Itself
If we know exactly how it is useful for the heartbeat or what benefits the breathing provides, the role of sleep is much more difficult to define. It is associated with the recovery, but also the strengthening of the memory of the day and the regulation of the immune system metabolism. Yet its function is crucial. Because insects to mammals, not forgetting the other animal species, everyone or almost sleeps. Men spend between a quarter and a third of their lives resting. Sleep has been shown to play a key role in setting memories and learning in the brain.
The brain weighs about 1,400 grams. It consumes around 300 kilocalories a day. It is a complex organ. It works like the motor of the body, but routine, daily stress, poor diet, sedentary life and lack of good sleep habits can affect it little by little. During daily operation, it generates chain symptoms: headaches, head, neck and back pain, blurred vision, buzzing, aching heart, anxiety, and even depression. For proper functioning, the walls of the arteries must be completely free of substances that prevent good brain circulation. These obstacles are toxins. One of them, prostaglandin causes inflammation of the arteries.
Several stimuli can generate this intoxication: visual impulses, spending a lot of time in front of a computer; auditory, the noise of vehicular traffic, the use of headphones at a loud volume; olfactory, very strong smells like gasoline or other chemicals; and taste stimuli, excessive consumption of processed food or canned and frozen products.
Just getting a good night’s sleep helps eliminate all that brain waste as it was revealed in the Rochester investigation. Thanks to the mouse brain imaging, the results showed that during sleep the glymphatic system of the brain became ten times more active than during the waking state. At the same time, the size of brain cells is reduced by about 60 percent. This creates more space between the cells, giving access to the cerebrospinal fluid to eliminate waste and toxic.
Like a janitor sweeping the corridors when the light goes out, in the brain, there are great changes during sleep that allow him to expel the garbage and ward off the disease. Until now, we did not fully understand that sleep responds to an essential and vital function of evolution.
The researchers wondered if there were any differences between sleep and waking in the blood system. Evacuating toxins can be difficult or ineffective if the brain receives sensory and other information.
The flow of cerebrospinal fluid and the size of the interstitial space increase during sleep, but to find out if the brain is able to eliminate more waste, they have injected the beta-amyloid protein into the dormant brain. the awakening of the mice. The glymphatic system evacuated the waste twice as fast in dormant brains as when it was awake.
During waking the brain is stimulated and active after the release of an organic compound called norepinephrine. This neurotransmitter is not very active during sleep, but it is released when the brain needs to be alert, for example, to fear and other external stimuli. The researchers suggest that norepinephrine may play a role in regulating gaps between brain cells.
All physiology changes during sleep. The novelty is the role of the interstitial space but it is only a new piece of the puzzle, not all the mechanisms. This shows once again that sleep can contribute to the restoration of brain cell function and may have protective effects.
This discovery could advance the understanding of the biological functions of sleep, explain why we spend a third of our lives sleeping and could find treatments for neurological diseases.
6 – A Dysfunction in the Cleaning System Is Linked to the Neuro-Degenerative Process
A study from the Autonomous University of Barcelona and the Ludwig Maximilian University in Munich, published in the journal Science Translational Medicine on July 2014, describes the molecular mechanism by which mutated forms of TREM2 protein prevent the process of waste cleaning.
This is the TREM2 protein whose reduced levels are associated with the risk of neurodegenerative diseases such as Alzheimer’s disease or other forms of dementia.
The TREM2 gene is expressed primarily in macrophage brain cells or in charge of phagocytosis and elimination of cellular waste, the microglial cells. Among the waste to be eliminated are the aggregates of proteins and amyloid fibers specific to Alzheimer’s disease.
The results suggest that the TREM2 protein plays a fundamental role in the elimination of amyloids and other protein aggregates and that its dysfunction accelerates neuro-degenerative processes.
7 – Do Not Sleep Would Destroy the Neurons
A study from the University of Pennsylvania School of Medicine and Peking University published by the Journal of Neuroscience in March 2014, reveals that lack of sleep could result in loss of neurons.
According to the researchers, this is the first time that it is proven that lack of sleep can lead to a loss of brain cells. These are the neurons locus coeuruleus. Their disappearance would accelerate the development of diseases such as Alzheimer’s or Parkinson’s.
The lack of sleep over a prolonged period is related to the damage, or the loss, of these neurons essential for vivacity and for optimal cognitive abilities.
This new study shows alarming evidence that chronic sleep loss may be more serious than previously thought, and could even lead to irreversible physical damage and loss of neurons.