On average humans spend a third of their lives sleeping (Underwood, 2013). Sleep deprivation had been shown to lead to poor decision-making, impaired learning and heightened risk of migraines and epileptic attacks. Even more severe, chronic and complete insomnia has been seen to result in death in humans (Herculano-Houzel, 2013). Yet for something so vital, scientists still do not know exactly why we sleep. A new study by Xie et al. provides the first experimental evidence on a molecular level that when we sleep our brains remove the waste products produced during cellular metabolism (Xie et al., 2013).
Neurons are extremely sensitive to their environments, which means that it is essential that toxic substances be removed immediately. It was previously assumed that toxins were degraded within the brain, because it lacks lymphatic vessels. In the rest of the body the lymphatic system removes interstitial waste, which is then transported to the liver via the blood and degraded (Xie et al., 2013). In the brain the newly discovered glymphatic system is responsible for the removal of waste products such as β-amyloids that can aggregate to form plaques (Underwood, 2013). Cerebrospinal fluid (CSF) is moved through the para-arterial space within the brain and is pumped into the interstitial space by glial (non-neural brain cells) astrocytic aquaporin-4 (AQP4) water channels. CSF exchanges with the interstitial fluid (ISF) that surrounds brain cells, forcing waste products along with the ISF into the para-venous space. The ISF and its constituents are taken out of the brain and able to exchange with the lymphatic system in the neck, this entire process can be see in Figure 1 (Nedergaard, 2013). It is believed that one of the reasons that this occurs when we sleep is due to the large amount of energy required to pump CSF through our brains (Underwood, 2013).
When asleep the interstitial space expands by up to 60%, taking approximately 20% or our total brain volume. This change in interstitial volume promotes the influx of CSF into the interstitial space resulting in the glymphatic systems ability to operate twice as fast (Xie et al., 2013). The variation in interstitial space is theorized to be caused by cells swelling due to an increase in extracellular potassium ion concentrations. Potassium increases as a result of neural activity stimulated by noradrenaline, which is only released during waking, and is removed when asleep. Therefore the need for sleep could be driven by the build up of noradrenaline concentrations in the interstitial space (Herculano-Houzel, 2013).
This new idea of sleep being induced by a build up of waste can also explain the unanswered question of why different species require varying numbers of hours of sleep. Bats require approximately 20 hours of sleep, whereas much larger animals such as elephants only need 3-4 hours. The ability of CFS to clear the interstitial space is limited to the volume of that space. This increases much more proportionally in larger brains than smaller ones, therefore smaller brains require more time to flush out the waste (Herculano-Houzel, 2013).
The build up of aggregates like β-amyloids has been seen to be a precursor to many neurodegenerative diseases such as Alzheimer’s disease. Symptoms of these diseases consistently include inconsistent sleep patterns (Underwood, 2013). Even if this is not the case, the need for sleep is evident, and the effect of sleep deprivation even clearer. So perhaps, there is a therapeutic target within the glymphatic system that could be used to treat a variety of health problems in the future.
References:
Herculano-Houzel, S. (2013). Neuroscience. Sleep it out. Science (New York, N.Y.), 342(6156), 316–7. doi:10.1126/science.1245798
Nedergaard, M. (2013). Neuroscience. Garbage truck of the brain. Science (New York, N.Y.), 340(6140), 1529–30. doi:10.1126/science.1240514
Underwood, E. (2013). Neuroscience. Sleep: the brain’s housekeeper? Science (New York, N.Y.), 342(6156), 301. doi:10.1126/science.342.6156.301
Xie, L., Kang, H., Xu, Q., Chen, M. J., Liao, Y., Thiyagarajan, M., … Nedergaard, M. (2013). Sleep drives metabolite clearance from the adult brain. Science (New York, N.Y.), 342(6156), 373–7. doi:10.1126/science.1241224