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Sunday, July 22, 2018

Good night. Sleep clean

Why do we need to rest? Meet your brain’s janitorial staff.

Updated: January 18, 2014 11:23:27 pm

Sleep seems like a perfectly fine waste of time. Why would our bodies evolve to spend close to one-third of our lives completely out of it, when we could instead be doing something useful or exciting? Something that would, as an added bonus, be less likely to get us killed back when we were sleeping on the savanna?

“Sleep is such a dangerous thing to do, when you’re out in the wild,” Maiken Nedergaard, a Danish biologist who has been leading research into sleep function at the University of Rochester’s medical school, said. “It has to have a basic evolutional function. Otherwise it would have been eliminated.”

We’ve known for some time that sleep is essential for consolidating memories and that it plays a central role in the formation of new neuronal connections and the pruning of old ones. But that hardly seems enough to risk death-by-leopard-in-the-night.

In a series of new studies, published this fall in the journal Science, the Nedergaard lab may at last be shedding light on just why sleep is important. As your body sleeps, your brain is quite actively playing the part of mental janitor: It’s clearing out all of the junk that has accumulated as a result of your daily thinking.

Recall what happens to your body during exercise. You start off full of energy, but soon enough your breathing turns uneven and your muscles tire. Your body isn’t able to deliver oxygen quickly enough to each muscle and instead creates energy anaerobically. And while that process allows you to keep on going, a side effect is the accumulation of toxic byproducts in your muscle cells. Those byproducts are cleared out by the body’s lymphatic system.

The lymphatic system serves as the body’s custodian. The brain, however, is outside its reach — despite the fact that your brain uses up about 20 per cent of your body’s energy.

Until a few years ago, the prevailing model was based on recycling: The brain got rid of its own waste, not only beta-amyloid but other metabolites, by breaking it down and recycling it. When that process eventually failed, the buildup would result in age-related cognitive decline and diseases like Alzheimer’s. That “didn’t make sense” to Nedergaard, who says that “the brain is too busy to recycle” all of its energy. Instead, she proposed a brain equivalent of the lymphatic system. She called it the glymphatic system, a nod to its dependence on glial cells (the supportive cells in the brain that work largely to maintain homeostasis and protect neurons) and its function as a sort of parallel lymphatic system.

She was hardly the first to think in those terms. “It had been proposed about 100 years ago, but they didn’t have the tools to study it properly,” she says. Now, however, with advanced microscopes and dyeing techniques, her team discovered that the brain’s interstitial space — the fluid-filled area between tissue cells that takes up about 20 per cent of the brain’s total volume — was mainly dedicated to physically removing the cells’ daily waste.

When the team injected small fluorescent tracers into the cerebrospinal fluid of anaesthetised mice, they found that the tracers quickly entered the brain — and eventually exited it — via specific, predictable routes.

The next step was to see how and when, exactly, the glymphatic system did its work. In a series of new studies on mice, her team discovered exactly that: When the mouse brain is sleeping or under anaesthesia, it’s busy cleaning out the waste that accumulated while it was awake.

Modern society is increasingly ill-equipped to provide our brains with the requisite cleaning time. Some 80 per cent of working adults suffer from sleep deprivation. On average, we’re getting one to two hours less sleep than we did 50 to 100 years ago. Between 50 and 70 million people in the United States suffer from some form of chronic sleep disorder. At the University of Pennsylvania’s Centre for Sleep and Circadian Neurobiology, Sigrid Veasey has been focusing on precisely how restless nights disturb the brain’s normal metabolism.

At the extreme end, the result could be the acceleration of neurodegenerative diseases. While we don’t know whether sleep loss causes the disease, or the disease itself leads to sleep loss — what Veasey calls a “classic chicken-and-egg” problem.

“To me,” says Veasey, “that’s the most compelling part of the Nedergaard research. That the clearance for these is dramatically reduced from prolonged wakefulness.”

In one set of studies, soon to be published in The Journal of Neuroscience, the Veasey lab found that while our brains can recover quite readily from short-term sleep loss, chronic prolonged wakefulness and sleep disruption stresses the brain’s metabolism.
Now that we have a better understanding of why sleep is so important, a new generation of drug makers can work to create the best possible environment for the trash pickup to occur.

A second approach would take the opposite tack. In response to the evolving data, future drug interventions could focus directly on the glymphatic system, to promote the enhanced cleaning power of the sleeping brain in a brain that is fully awake.
If that day comes, in Veasey’s joking words, “it could mean we never have to sleep at all.”

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