The brain has its own washing machine to clear out waste products known as the glymphatic system. We’ve known about it for a while, but nobody was exactly sure what was driving the system – until now. New research studying mice has uncovered how a molecule called norepinephrine plays a key role in “brainwashing” mice while they sleep, and it could have significant implications for human sleep and the use of sleep aids, too.

The brain is a very busy organ and as it works, it accumulates toxic proteins that can cause sticky plaques. These plaques have been linked to several neurological disorders, including Alzheimer’s, but the brain has an inbuilt system for clearing out troublesome toxic proteins: the glymphatic system.

It’s long been thought that one of the crucial functions of sleep is enabling the glymphatic system to get to work, circulating fluid in the brain and spinal cord to effectively flush out toxic proteins. However, questions remained as to how it all worked.

“It’s like turning on the dishwasher before you go to bed and waking up with a clean brain,” said senior author Maiken Nedergaard of the University of Rochester and the University of Copenhagen in a statement. “We’re essentially asking what drives this process and trying to define restorative sleep based on glymphatic clearance.”

Nedergaard and colleagues used a mouse model to investigate what happens to the brain during sleep, focusing specifically on the role of norepinephrine and blood flow during the deep sleep phase. What they saw was that during deep sleep, the brainstem of a mouse releases waves of norepinephrine roughly every 50 seconds. That release triggered a rhythmic pulsation of blood vessels, causing the surrounding fluid to flow in a way that could sweep away waste products.

“You can view norepinephrine as this conductor of an orchestra,” added lead author Natalie Hauglund of the University of Copenhagen and the University of Oxford. “There’s a harmony in the constriction and dilation of the arteries, which then drives the cerebrospinal fluid through the brain to remove the waste products.”

The waves of the norepinephrine correlated with variations in brain blood volume, indicating that the movement of the vessels effectively acts like a pump, switching on the brain’s “dishwasher”. 

While the results are based on mice, they may carry insights that could be useful for studying sleep in humans, and one area the researchers are particularly interested in is the possible influence of sleep aid medication.

“More and more people are using sleep medication, and it’s really important to know if that’s healthy sleep,” said Hauglund. “If people aren’t getting the full benefits of sleep, they should be aware of that so they can make informed decisions.”

We know humans also have a glymphatic system and previous research has revealed that we see similar fluctuations in brain blood flow, fluid, and release of norepinephrine, but more research is needed to see if what this study observed in mice applies to our own species. Furthermore, a separate study into mice concluded that glymphatic clearance was actually less efficient during sleep, but it’s worth noting this was met with some controversy when it was published.

Much still to do, but for a worthy cause, as it’s hoped that by better understanding what humans need to get a good night’s rest, we may be able to take a preventative approach to neurological disorders like Alzheimer’s disease, the risk of which can sometimes be higher in people who don’t sleep well.

“Now we know norepinephrine is driving the cleaning of the brain, we may figure out how to get people a long and restorative sleep,” Nedergaard concluded.

The study is published in the journal Cell.