Sci & Tech Editor Francesca Benson explains a proposed system for waste removal in the brain and how it could be linked to sleep

Science and Technology Editor, final year Biochemistry MSci student twitter.com/chessbenson
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Sleep, whether it is a full eight hours or just a twenty-minute power nap, is an essential part of life. However, as you lay your head down to rest, do you ever ask yourself why we need to be unconscious for an extended period of time every day? The brain is not inactive during this time, it is in fact undergoing processes which are key for proper brain function. One process is suggested to be strengthening or removing neural connections depending on whether or not they are needed. Another potential system in the brain that has been linked to sleep is the glymphatic system. This could be how the brain clears waste, including proteins associated with diseases such as Alzheimer’s. 

the glymphatic system… could be how the brain clears waste

The usual way the body removes waste and excess fluid from tissues is via the lymphatic system. Tissue cells are surrounded by interstitial space which is filled with interstitial fluid (ISF). ISF contains many things, like cellular waste and blood plasma forced out of capillaries due to pressure. ISF enters the lymphatic system via lymphatic vessels, then filtered through lymph nodes where infection is detected and fought by immune cells. It is then returned to the bloodstream, and waste proteins transported to the liver to be degraded.  

The central nervous system is made up of the brain and spinal cord. Unlike the rest of the body, the central nervous system does not have lymphatic vessels. The central nervous system must therefore remove waste and balance fluid levels by other means. One proposed model is the glymphatic pathway. It is called this because it is linked to cells known as glia, specifically a type called astrocytes. These have a water channel known as aquaporin-4, suggested to affect the movement of water and drive the movement of cerebrospinal fluid in the brain.

Unlike the rest of the body, the central nervous system does not have lymphatic vessels

Cerebrospinal fluid (CSF) surrounds the central nervous system, acting as a shock absorber. In the glymphatic pathway, CSF enters the brain in spaces surrounding arteries, then moves through the interstitial space in the brain. This influx of CSF drives ISF to be flushed out. ISF drains out of spaces surrounding veins exiting the brain, taking waste and debris with it into the lymphatic system. The debris includes proteins such as amyloid beta which forms the plaques in the brains of those with Alzheimer’s disease, and alpha-synuclein which is misfolded in those with Parkinson’s disease.

In mouse studies, data suggests that during natural sleep or anaesthesia the interstitial space in the brain expands by around 60%. Influx into the glymphatic system was massively reduced – by around 95% – in mice that were awake rather than asleep. This indicates that the glymphatic system is a lot more active during sleep. This pathway has been demonstrated in mouse models, but whether it is present in humans has yet to be fully confirmed. Recent MRI studies have provided evidence that supports the theory that humans have a glymphatic system, and multiple studies have demonstrated that lack of sleep can increase levels of amyloid beta in human brains. So maybe next time you consider pulling an all-nighter, get some rest instead to help your brain recuperate.

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