Researchers at the University of Rochester Medical Center have found that a recently discovered system that flushes waste from the brain is primarily active during sleep.
“This study shows that the brain has different functional states when asleep and when awake,” said Maiken Nedergaard, M.D., D.M.Sc., co-director of the University of Rochester Medical Center’s Center for Translational Neuromedicine and lead author of the study.
“In fact, the restorative nature of sleep appears to be the result of the active clearance of the byproducts of neural activity that accumulate during wakefulness.”
The study, published in the journal Science, reveals that the brain’s unique method of waste removal — known as the glymphatic system — is very active during sleep, clearing away toxins responsible for Alzheimer’s disease and other neurological disorders.
The researchers also found that during sleep the brain’s cells reduce in size, allowing waste to be removed more effectively.
The new findings are a result of the discovery last year by Nedergaard and her colleagues of a previously unknown system of waste removal that is unique to the brain.
The system responsible for disposing cellular waste in the rest of the body, the lymphatic system, does not extend to the brain, the researcher noted. This is because the brain maintains its own closed “ecosystem” and is protected by a complex system of molecular gateways — known as the blood-brain barrier — that controls what enters and exits the brain.
Using new imaging technologies, namely two-photo microscopy, the scientists were able to observe in mice — whose brains are remarkably similar to humans — what amounts to a plumbing system. It pumps cerebral spinal fluid (CSF) through the brain’s tissue, flushing waste back into the circulatory system where it eventually makes its way to the general blood circulation system and, ultimately, the liver.
The timely removal of waste from the brain is essential, where the unchecked accumulation of toxic proteins such as amyloid beta can lead to Alzheimer’s disease, the researchers explain. In fact, almost every neurodegenerative disease is associated with the accumulation of cellular waste products, researchers add.
One of the clues that the glymphatic system may be more active during sleep was the fact that the amount of energy consumed by the brain does not dramatically decrease while we sleep, the researchers explain. Because pumping CSF demands a great deal of energy, researchers speculated that the process of cleaning may not be compatible with the functions the brain must perform when we are awake and actively processing information.
Through a series of experiments in mice, the researchers observed that the glymphatic system was almost 10-fold more active during sleep — and that the sleeping brain removed significantly more amyloid-beta.
“The brain only has 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,” said 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.”
Another finding that startled the researchers was that the cells in the brain “shrink” by 60 percent during sleep. This contraction creates more space between the cells and allows CSF to wash more freely through the brain tissue, they said.
The researchers said they also observed that a hormone called noradrenaline is less active in sleep. This neurotransmitter is known to be released in bursts when the brain needs to become alert, typically in response to fear or other external stimulus.
The researchers speculate that noradrenaline may serve as a “master regulator” controlling the contraction and expansion of the brain’s cells during sleep-wake cycles.
“These findings have significant implications for treating ‘dirty brain’ disease like Alzheimer’s,” said 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.”