We've all experienced the grinding headache and bodily misery that comes from a few nights of not enough sleep. But why does a sleep deficit wreak such havoc with your normal functioning? New research suggests that sleep fulfills a vital function, and missing sleep can ruin you, even worse than you already suspected.


In a nutshell, this new study provides evidence that we need a certain amount of sleep every night, because the brain takes this time to rid itself of toxic metabolic byproducts, which would otherwise accumulate in the brain and impair brain function, destroy neurons — and potentially cause neurodegenerative disorders.


One of the main functions of the lymphatic system is to remove the body of waste. A fluid called lymph bathes the cells and tissues in the body, collects cellular waste products and dumps them back into the bloodstream to be filtered from the body.

But the brain has no lymphatic vessels. It has its own internal ecosystem and is surrounded by the blood-brain barrier, which controls what enters and leaves the organ. These features have long been a conundrum for scientists.

"Since the brain has a very high metabolic rate, how does it efficiently remove metabolic waste that's produced between cells?" says Rashid Deane, a researcher with the University of Rochester Medical Center.

The Glymphatic System

Last year, Deane and his colleagues discovered that the brain has its own special garbage disposal system, which they've dubbed the glymphatic system, named after the glial cells that are involved in the waste disposal process and the lymphatic system. The glymphatic system is made up of star-shaped glial cells called astrocytes, which form a network of water channels surrounding the brain's blood vessels.


Cerebrospinal fluid (CSF) flows into the brain along the channels that surround the arteries. The fluid then washes through the brain tissues and intermixes with the waste-filled interstitial fluid that surrounds the cells of the brain. Finally, the CSF collects in the channels around the veins and drains out of the brain, taking the metabolic waste with it.


Importantly, the team discovered that the glymphatic system is responsible for clearing the brain of amyloid beta — a metabolite that many researchers believe can lead to Alzheimer's disease if it builds up and destroys neurons. This suggests that Alzheimer's disease may arise because of a faulty glymphatic system.

In fact, the researchers showed that removing the water channels in mice causes amyloid beta to build up in the brain.


Sleeping to Take Out the Trash

With that research complete, Deane and his colleagues then wondered if there are differences in the glymphatic system between sleeping and waking states. "While you're awake, brain cells are all fired up and producing waste products, but they need to clear those products, too," Deane tells io9. Waste clearance may be difficult or inefficient if the brain is taking in sensory and other information.


Additionally, scientists have previously discovered that amyloid beta levels are higher during wakefulness, compared with sleep. On one hand, this change could mean that the production of the metabolite and others are different while you're asleep. Alternatively, it could mean that the brain just disposes of its waste better while you're asleep.

To test this latter idea, the researchers trained mice to relax and fall asleep on a device called a two-photon microscope, which can trace the movement of dyes through living tissue in high resolution. Once the mice fell asleep — which the researchers could tell based on the rodents' brain activity — they injected a green dye into their CSF. After half an hour, they woke the mice up, and then injected a red dye into the CSF. By tracking the movement of the two dyes during the session, the researchers discovered that the flow of CSF through the interstitial space — the gaps between the cells — during waking is only about five percent of what it is during sleep.


Next, the researchers decided to test whether this interstitial space is increased during sleep — which could possibly explain the increase in CSF flow. "If the gaps between cells are wider, then there will be a larger channel for the fluid to flow through," Deane explains.

In the waking mouse brain, the interstitial space makes up 13 to 15 percent of the brain's volume, the researchers found. But when the mouse is sleeping, this space increases to between 22 and 24 percent. The team isn't sure why the space increases during sleep, but they theorize that the brains cells actually shrink.


So the flow of CSF and the size of the interstitial space both increase during sleep — but does this actually mean the brain is able to clear away more debris? To find out, Deane and his colleagues injected amyloid beta into the brains of sleeping and waking mice. The glymphatic system cleared the waste twice as fast in the sleeping brains than in the waking brains.


Finally, the researchers sought to determine what drives these changes in interstitial space volume that lead to greater waste clearance. "We know that during waking, the brain gets fired up and active after the release of a chemical called noradrenaline," Deane said. This neurotransmitter is not very active during sleep, but it gets released in bursts when the brain needs to be alert, such as in response to fear and other external stimuli.

The scientists used an inhibiter to block noradrenaline in the brains of waking mice, causing their brain activity to become more "sleep-like." Inhibiting the chemical also caused the brains' interstitial volume to jump from 14.3 percent to 22.6 percent. The researchers suggest noradrenaline may play a role in regulating the gaps between cells in the brain.


The Link To Neurodegenerative Diseases

Alzheimer's disease and other neurodegenerative diseases are associated with not only the buildup of waste products, but also lack of sleep. While the team's previous study suggested glymphatic failures might be behind neurodegenerative diseases, the current study suggests lack of sleep could be an additional culprit. Specifically, if someone consistently doesn't get enough sleep, amyloid beta and other waste could build up in the brain and destroy neurons, leading to dementia.


"Both failure of the glymphatic system and lack of sleep could ultimately lead to increased waste products," Deane said.

The implications of the study are huge, especially when you consider that 50 to 70 million adults in the United States alone have a sleep or wakefulness disorder, according to the Centers for Disease Control and Prevention. There are a number of different drugs out there to help induce sleep, but future therapies could also help the brain clear out its waste products, Deane said.


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For now, the researchers want to figure out just how the interstitial space increases or decreases with changing brain states. But there many other interesting questions to investigate.

For example, it's well known that sleep deprivation decreases your cognitive functions — could this impairment actually be due to the accumulation of brain waste? And could the buildup of waste even be what makes us sleepy and drives us into our beds at the end of the day?


Read the full paper containing the team's findings in the journal Science.

Top image via bark/Flickr. Inset image via Suzana Herculano-Houzel/Science.