How Your Brain “Takes Out The Trash” While You Sleep

For centuries, sleep has been more of a mystery to evolution than the duckbill platypus. Yet despite its weirdness, like every animal, even the platypus needs its zzz’s. Considering this unconscious function has been conserved across species and the fact that our brains are just as active during sleep as in wakefulness, scientists have been searching for whatever it is about this horizontal trip into the unknown that makes it so important to survival.

In a report published in the journal Science, Lulu Xie and her colleagues may have stumbled upon an answer. It turns out, at least in mice, sleep is an off-hours time for the janitors of the brain to do some major cleaning.

What’s going on in there? External threats aren’t the only things our bodies need to detect and control. Internal threats, like the proteins that build up in the interstitial fluid surrounding our cells, can be dangerous, especially certain ones in the brain linked to neurodegenerative diseases like Alzheimer’s. We must remove these proteins to stay healthy. In the brain, the “glymphatic system” does the dirty work through the interchange of cerebral spinal fluid (CSF) and interstitial fluid (ISF). When an animal is awake, there is a higher concentration of these “dirty” proteins than when asleep. Could sleep play a role in managing their disposal?

Researchers in this report first turned to CSF influx in the brains of mice in different states of consciousness: sleep, awake, anesthetized. They used a fancy microscope to visualize a fluorescent tracer they had injected into the brains of living animals, to follow the flow of CSF in real time. They saw less CSF influx in awake mice, which just meant that it was harder for CSF to get in and make that exchange with fluids in the interstitial space and implied a less efficient glymphatic system during wakefulness. Imagine moving through a crowded bar or shopping mall on Black Friday. It’s tough to get through the crowd. In the brain, the same thing was happening. Wakefulness constricted the interstitial space and limited CSF influx.

Perhaps because of more CSF influx during sleep, the glymphatic system was more efficient at removing those “dirty” proteins mentioned earlier. Xie’s team proved this was the case by literally injecting these proteins into the brains of sleeping, anesthetized and awake mice and counting how many were left as time passed. Finding fewer proteins sooner in the sleeping brain than the awake, they knew something was causing it to clear them twice as fast.

That something was a neuromodulator, norepinephrine. It helps regulate arousal and control cell volume in the heart and kidney. By blocking norepinephrine, the researchers drove the awake mice into a sleep-like state and increased the volume of interstitial space. More space to move meant more CSF influx, and that meant a better environment for cleaning.

With new light gleaned on the function of sleep, I can’t help but wonder if it works the same way in that anomaly of an animal, the duckbill platypus.

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