Brain cleans itself during sleep

Scientists said Thursday they have found what could be sleep's basic purpose: it clears the brain of toxic metabolic byproducts. The findings, published in the US journal Science, revealed that the brain's unique method of waste removal, dubbed the glymphatic system, is highly active during sleep, clearing away toxins responsible for Alzheimer's disease and other neurological disorders. Researchers from the University of Rochester, New York, also found that during sleep the brain's cells reduce in size, allowing waste to be removed more effectively. "This study shows that the brain has different functional states when asleep and when awake," said Maiken Nedergaard of the University of Rochester Medical Center and senior author of the study. The purpose of sleep is a question that has captivated both philosophers and scientists since the time of the ancient Greeks. While recent findings have shown that sleep can help store and consolidate memories, these benefits do not appear to outweigh the accompanying vulnerability, leading scientists to speculate that there must be a more essential function to the sleep-wake cycle. The new findings hinged on the discovery last year by Nedergaard and her colleagues of the glymphatic system, a previously unknown system of waste removal that is unique to the brain. The system acts like a plumbing system that piggybacks on the brain's blood vessels and 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 researchers said. They speculated the glymphatic system may be more active during sleep because the amount of energy consumed by the brain does not decrease dramatically when people are at sleep. In order to prove their idea, Lulu Xie, the study's first author, spent two years in training mice to relax and fall asleep. Once Xie was sure the mice were asleep, she injected a green dye into their CSF through a catheterlike device in their necks. After half an hour, she awakened them by touching their tails and injected a red dye that the two-photon microscope could easily distinguish from the green. By tracking the movements of red and green dye throughout the brain, the researchers found that large amounts of CSF flowed into the brain of the mice during sleep, but not during the awake state. In all, the glymphatic system was almost 10-fold more active during sleep, they said. One waste product removed by the system during sleep is - amyloid, a protein implicated in Alzheimer's disease. The researchers tagged -amyloid with fluorescent tags and made the observation. They found in sleeping mice, the tags flowed out of the brain twice as fast. Another startling finding 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, the researchers said. "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."