Sara Reardon in Science: We all need sleep, but no one really knows why. For the past 10 years, a prevailing theory has been that a key function of sleep is to wash waste products and toxins from the brain via a series of tiny channels called the glymphatic system. Sleep problems can disrupt this process, the theory’s proponents say, perhaps raising the risk of Alzheimer’s disease and other brain disorders. Mouse experiments seem to support the idea. But in recent years, several groups of scientists have challenged some aspects of the theory. Now, a new study has found that the mouse brain clears small dye molecules more efficiently while the animal is awake than when it is asleep or under anesthesia. A glymphatic system might still cleanse the brain, the researchers say, but sleep actually slows this cleansing down.
Other researchers are stumped as to how to explain the opposing results, and several declined to comment on the record for fear of entering a heated debate. A few see the new findings as a serious blow to the sleep clearance theory, but others say the new paper’s methods are too different from those of the earlier work to credibly challenge it. “When you criticize a concept that has been there for some time, then your design should be even better,” says Per Kristian Eide of the University of Oslo.
In the original mouse experiments, neuroscientist Maiken Nedergaard at the University of Rochester and her team injected a dye into the cisterna magna, a fluid-filled pocket at the back of the neck, which sits just outside the brain and supplies it with cerebrospinal fluid (CSF). They used a two-photon microscope to measure the influx of the dye to the brain and its spread through the organ. The influx increased when mice were asleep or under anesthesia compared with when they were awake, allowing the dye to penetrate through the brain. That led the researchers to conclude that more fluid was flowing through the brain and draining into blood or lymphatic vessels. Nedergaard proposed that this efflux relied on the pumping of fluid through tiny glymphatic vessels between neurons, which her team had identified in an earlier study.
Nicholas Franks, an anesthesia researcher at Imperial College London and senior author of the new paper, didn’t set out to disprove this popular hypothesis. “I really liked this sort of theory of sleep,” he says, “as a basic housekeeping mechanism that keeps the brain healthy and fully functional.” But he questioned whether the influx of dye was a reliable proxy for efflux, which he says would be impossible to measure directly by tracking every blood or lymphatic vessel or potential exit point from the brain.
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