Disease-causing waste that builds up during the day is cleaned out from our brain as we sleep at night, say researchers.
Their findings, published today in the journal Science, could help explain why people spend a third of their lives asleep, and may help in developing treatments for Alzheimer's disease and other neurological disorders.
"This study shows that the brain has different functional states when asleep and when awake," says study leader Dr Maiken Nedergaard from the University of Rochester Medical Center in New York.
"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."
In lab experiments on mice - whose brains are remarkably similar to humans - Nedergaard and colleagues observed how cellular waste was flushed out via the brain's blood vessels into the body's circulatory system and eventually the liver.
These waste products included amyloid beta, a protein that, when accumulated, is a driver of Alzheimer's disease.
Plumbing system
The researchers say waste is removed from brain tissue by cerebral spinal fluid (CSF) flushed through a 'plumbing system' called the glymphatic system, which appears to be nearly 10 times more active during sleep than while awake.
In their study Nedergaard and colleagues first injected dye into the CSF of mice and watched it flow through their brains, while simultaneously monitoring electrical brain activity. They found the dye flowed rapidly when the mice were unconscious, either asleep or anesthetised, but when the same mice were awake it barely flowed at all.
"We were surprised by how little flow there was into the brain when the mice were awake," says Nedergaard. "It suggested that the space between brain cells changed greatly between conscious and unconscious states."
To test this idea, the researchers used electrodes inserted into the brain to directly measure the space between brain cells.
They found that during sleep, the brain's cells shrink by about 60 per cent, opening up the brain's interstitial space and allowing the fluid to move faster and more freely through it.
Energy use
Nedergaard and colleagues say the amount of energy consumed by the brain does not decrease dramatically while we sleep.
Because pumping CSF demands a great deal of energy, they speculate that the process of cleaning may not be compatible with the functions the brain must perform when we are awake and actively processing information.
"The brain only has limited energy at its disposal," says Nedergaard. "You can think of it like having a house party. You can either entertain the guests or clean up the house, but you can't really do both at the same time."
During the study the researchers also injected labelled amyloid beta proteins into the brains of the mice and found that during sleep CSF cleared away this dirt outside of the cells twice as quickly.
"These findings have significant implications for treating 'dirty brain' disease like Alzheimer's," says Nedergaard. "Understanding precisely how and when the brain activates the glymphatic system and clears waste is a critical first step in efforts to potentially modulate this system and make it work more efficiently."
Co-authors of the study, which was funded by the US National Institutes of Health, came from Oregon Health and Science University and New York University.
