In a Study on Mice, Scientists Show How the Brain Washes Itself During Sleep

While you sleep, your brain runs some maintenance, including ridding itself of waste. Now, scientists have identified how this “rinsing” happens in mice brains—and since we have a similar rinsing system, the research could have important implications for human brains, as well. Their study was published in the journal Cell on Wednesday.

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

Nedergaard and other colleagues discovered the glymphatic system—responsible for waste-removal in the brain—in 2012. The glymphatic system moves a clear liquid called cerebrospinal fluid around the brain to flush out toxic proteins accumulated during waking hours. A 2013 study suggested that the rinsing takes place particularly during sleep, though more recent research challenged this by hypothesizing that the process is faster during waking hours. Either way, scientists didn’t understand how the waste-removal system might be driven during sleep—until now.

The new study reveals that, during a mouse’s non-rapid eye movement (non-REM) sleep, the brainstem releases waves of norepinephrine (a known hormone similar to adrenaline) about every 50 seconds, which causes blood vessels to tighten. This also creates a pulsing pattern, which generates oscillating blood volume, that, in turn, drives the brain fluid flow that washes away the toxins. Simply put, the norepinephrine triggers a pump-like effect that pushes fluid around the brain to rinse waste buildup.

“It is the oscillatory constriction-dilations that drive glymphatic flow,” Nedergaard explains to Popular Science’s Tom Hawking.

“We have identified maybe the most important driver of glymphatic flow in non-REM sleep,” Nedergaard tells Science’s Mitch Leslie. According to the study, the correlation between the release of norepinephrine and changes in brain blood volume was stronger during the restful non-REM sleep than during the more active REM sleep or waking hours.

The team then tested the impact of Zolpidem (a common sleep medication also known as Ambien or Zolpimist) on this system, and found that the norepinephrine waves during sleep decreased by 50 percent and fluid transport into the brain decreased by around 30 percent in zolpidem-treated mice. These results suggest that sleeping aids that impact norepinephrine production—which includes most sleeping aids—might harm the brain’s waste-removal system.

“Human sleep architecture is still fairly different than a mouse, but we do have the same brain circuit that was studied here,” Laura Lewis, a neuroscientist at Massachusetts Institute of Technology who was not involved in the study, tells New Scientist’s Grace Wade. “Some of these fundamental mechanisms are likely to apply to us as well.”

"More and more people are using sleep medication, and it's really important to know if that's healthy sleep," lead author Natalie Hauglund, a neuroscientist from the University of Copenhagen and the University of Oxford, says in the statement. "If people aren't getting the full benefits of sleep, they should be aware of that so they can make informed decisions."

Further research on this topic could shed light on how to help people attain healthy sleep, as well as provide insight into neurological disorders linked to the toxic proteins normally rinsed from the brain.

Margherita Bassi | READ MORE

Margherita Bassi is a freelance journalist and trilingual storyteller. Her work has appeared in publications including BBC Travel, Discover magazine, Live Science, Atlas Obscura and Hidden Compass.