It’s no secret that too little shut-eye can drain your brain, but scientists haven’t fully understood why.
Now, a new study suggests that a good night’s sleep leaves you feeling sharp and refreshed because a newly discovered system that scrubs away neural waste is mostly active when you’re at rest.
It’s a revelation that could not only transform scientists’ fundamental understanding of sleep, but also point to new ways to treat disorders such as Alzheimer’s disease, which are linked to the accumulation of toxins in the brain.
“We have a cleaning system that almost stops when we are awake and starts when we sleep. It’s almost like opening and closing a faucet -- it’s that dramatic,” says Dr. Maiken Nedergaard, co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center.
Nedergaard is the lead author of the study published Thursday in the journal Science. She and her colleagues first reported last year their discovery of the brain’s unique waste removal system, dubbed the glymphatic system. It works like a neural trash truck, clearing away toxic by-products that build up when you’re awake.
The scientists had used two-photon microscopy — a new imaging technology that allows scientists to see deep inside living tissue — to peer into the brains of mice, which are remarkably similar to human brains.
They found that the glymphatic system pumps cerebral spinal fluid, CSF, through the spaces around the brain cells, flushing waste into the circulatory system, where it eventually makes its way to the liver.
Their latest research, also in mice, used the same technology to focus on the timing of the glymphatic system. The researchers discovered that during sleep brain cells contract, increasing the space between the cells by as much as 60 percent and allowing the spinal fluid to wash more freely through the brain tissue.
“This study shows that the brain has different functional states when asleep and when awake,” Nedergaard says. “In fact, the restorative nature of sleep appears to be the result of the active clearance of the by-products of neural activity that accumulate during wakefulness.”
The scientists found that the glymphatic system was almost 10 times more active during sleep than when awake.
“The brain has only limited energy at its disposal and it appears that it must choose between two different functional states — awake and aware or asleep and cleaning up,” Nedergaard said. “You can think of it like having a house party. You can either entertain guests or clean up the house, but you can’t really do both at the same time.”
One of the waste products of the brain is the protein amyloid-beta, which accumulates and forms plaques in the brains of Alzheimer’s patients. Researchers at Washington University in St. Louis had previously shown that levels of amyloid-beta in mice brains dropped during sleep because of a decrease in production of the protein.
“That was an observation that inspired our work,” says Nedergaard, “and we decided to look at clearance.”
Both lower production of amyloid-beta and faster clearance are likely key to lower levels of amyloid-beta during sleep, says Nedergaard. Her view is echoed by Dr. Yo-El Ju, a professor of neurology and a member of Washington University’s research team.
“Possibly there are both mechanisms working that produce the large variations between wake and sleep that we see,” says Ju.
Patients with diseases that cause progressive brain decline — Alzheimer’s, Parkinson’s and Lewy Body dementia — often sleep poorly. The diseases are also associated with the abnormal buildup of protein in the brain.
While researchers don’t yet know if these plaques are a cause or a result of neurodegenerative disease, the new insights about the way sleep clears waste from the brain could lead to new treatment approaches, according to both Ju and Nedergaard.
“In addition to trying to decrease the amount of amyloid-beta production, perhaps we can also try to increase the amount of clearance,” says Ju.
Nedergaard and colleagues are testing possible drugs in mice that could do that.
“Understanding how and when the brain activates the glymphatic system and clears waste is a critical first step in efforts to potentially modulate the system and make it work more efficiently,” Nedergaard says.
Research in humans has shown that levels of amyloid-beta decline during sleep, as it does in mice, but it’s not yet known if the mechanisms are the same as in mice.
“Those experiments in humans to measure both production and clearance during wake and sleep are ongoing. We don’t have the results yet,” says Ju.
JoNel Aleccia of NBC News contributed to this report.