Short Wave - The Brain Makes A Lot Of Waste. Here's How It Cleans Itself Up

Episode Date: July 22, 2024

Scientists have long studied the relationship between sleep and the brain, and why poor sleep is linked to neurological diseases like Alzheimer's. NPR science correspondent Jon Hamilton talks to host Regina G. Barber about the brain's washing system and the particular sound researchers have found that seems to turn it on in mice. Read Jon's full piece here.Interested in more science about the brain? Email us at [e-mail] pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences.NPR Privacy Policy

You're listening to Shortwave from NPR. Hey, Short Wavers, Regina Barbara here, and it's time to talk about brainwashing. But not the kind you get in a cult. We're going to talk about how the brain literally washes itself. NPR science correspondent John Hamilton has been covering the latest research. Hey, John. Hey, Gina. So what kind of waste does the brain need to get rid of?

A lot of it is just stuff left over from all the processes that keep cells alive. So, for example, cells combine oxygen with glucose to make energy that produces water and carbon dioxide. And the cells need to get rid of that. Cells also need to clear away these toxic proteins like beta amyloid, which can form these sticky plaques in the brain that are a hallmark of Alzheimer's, which is, of course, that disease that gradually erodes your memory and thinking. Right. So maybe that disease is coming from all that garbage kind of getting built up in your brain? That is the idea. That is what most scientists believe right now. How does stuff build up in the brain? Well, it can build up in two places. It can build up inside of cells, which is what happens with tau protein, which is one of the proteins involved in Alzheimer's.

It can also build up in the fluid that's between cells, this interstitial fluid, and that's where amyloid plaques form, you know, those plaques that are associated with Alzheimer's. And when either of these things happens, it's really bad for the brain. In the short term, it can mean. that your neurons just don't work as well. So you're thinking and memory focus, they aren't as good. Long term, the accumulation of toxic proteins can actually damage or kill off neurons, which is exactly what happens in Alzheimer's and in other forms of dementia. That's not good. So how does my brain, your brain, our brains, clean themselves? That really wasn't clear until about 2012, 2013. That was when a team led by a Danish scientist named Micah Nettergard showed that, in mice, at least, something really amazing happens in the brain during sleep.

I talked to her back then, and she told me that during sleep, during deep sleep, they saw this dramatic change in the system that circulates cerebrospinal fluid through the brain. It was pumping fluid into the brain and removing fluid from the brain in a very rapid pace. It's like a dishwasher. It's floating by all the cells which are the dishes and washing them. Wow, that's so cool. I love the visual. Right. And so for the past decades, science have been trying to understand precisely how that system works in people. The idea is that if you could sort of turn on the washing machine every now and then, you might be able to prevent Alzheimer's or other brain diseases. And there have been some hints that they are close to finding a switch that does that. So today on the show, how brain washing helps keep diseases away.

And why this sound might start the washing process. You're listening to Shortwave, the science podcast from NPR. Okay, so we're talking about how the brain gets rid of waste. Is that different than what happens in the rest of the body? It is. The body has something called the lymphatic system. It's this network of tiny tubes. They run alongside blood vessels.

And one of the things that this system does is carry waste away from cells, you know, into the bloodstream. And ultimately, you know, it carries it to organs like the liver and kidneys, which send the bad stuff out of your body. But the brain lives in this kind of protected space that doesn't really have a lymphatic system. So that's why it was really a big deal when researchers discovered this washing machine thing that seemed to be happening during sleep. By the way, they named it the glymphatic system, glymphatic with a G. Okay. That is a mashup of glia, a kind of brain cell that's central to the process. And lymphatic.

Glea, lymphatic, glymphatic. I love it. So scientists find this dishwasher in the brain. What happens next? One thing, they needed to figure out whether the glimphatic system explained something that scientists have been wondering about for a really long time. And that is the relationship between sleep and brain diseases like Alzheimer's. Researchers have known for a very long time that people with Alzheimer's typically don't sleep very well. But there's this chicken and egg question. Does Alzheimer's cause sleep problems or do sleep problems cause Alzheimer's?

Or could it work both ways, right? So researchers wanted to know whether they could show that bad sleep messes up the waste removal system, causing toxins to build up in a way that causes Alzheimer's. Yeah, how do they go about studying that? In mice, it was pretty straightforward. Researchers took some mice that are predisposed to develop Alzheimer's. They disrupted their sleep, and then they watched to see what happened. And sure enough, the glymphatic system didn't work as well.

And the little mouse brain started accumulating these toxic proteins. teens that are associated with Alzheimer's. Wow. Okay. The thing is, mice don't really get Alzheimer's the way people do, and their brains are really different from ours. So, flash forward to 2017, scientists at Washington University in St. Louis had a group of healthy people go to sleep in a lab.

Then when their brain started producing these slow waves that indicate they're going into this stage of deep sleep, the researchers would set off this loud beep and like wake them up. Oh, my God. That's so mean. Right? And they did this to half of the people in the study for an entire week. Then during the next week, they started beeping the other half of the people who'd been allowed to sleep the week before. And what this experiment showed pretty clearly was that when you interrupt deep sleep, the brain doesn't wash itself as well.

And levels of amyloid beta and another toxic protein called tau, they go up. But we already knew that getting good sleep in one way does keep your brain healthy. So is there any other way to switch on this dishwasher in the brain, like a drug or some sort of like therapy? Yeah, that has been one of the big questions. But to find another switch, researchers really had to understand better what was happening during sleep that fired up this glymphatic system. There was this big advance that happened in 2019. That's when a scientist named Laura Lewis, she was at Boston University. Now she's at the Pekauer Institute at MIT.

what Laura's team did was find a way to watch the entire process happen in the brains of 11 people as they slept. She told me that when people enter deep sleep, these slow electrical waves would start appearing in the brain. First, we would see a slow wave happening, which usually corresponds to many neurons going quiet all at the same time. And then after that, we would see a drop in the blood oxygenation level that we detect across the whole kind of surface of the brain. And then after that, we would see this wave of fluid flowing into the brain. And all of this was unfolding over several seconds. What was the fluid? Like, walk me through which she just said.

What she's talking about is this kind of pulsation that you can see in the brain. So first, you have the appearance of these slow electrical waves. Then brain cells kind of shut down for a moment. They actually shrink. The other research has shown. And then there's this rush of fluid into the brain. And it's kind of like watching one of those old ham pumps on a well. And that brings us to the very latest news on the brain's dishwasher and how it can be turned on or off.

So in early 2024, two papers were published simultaneously in the journal Nature. And together, they kind of seal the deal on this glymphatic system, or at least that's the way it seems. One paper was from Jonathan Kipnis at Washington University in St. Louis. he led his team that wanted to know whether the slow electrical waves were turning brain cells literally into tiny pumps that could physically push fluid from deep in the brain out toward the surface. Could it be that this neural activity, which is synchronized at night by itself releases enough force to push the flow through the brain? And to answer this, we were able to silence neural activity in particular brain region. And that brain region was not washed. And then we need other way around.

We enhanced those waves. And now we saw more efficient a clearance of that brain region. I'm still confused on what this fluid is. There are two kinds of fluid. There is what they call interstitial fluid, which is the fluid between the cells in the plane, between neurons, right? And somehow that fluid has to interact with what is called cerebrospinal fluid, which is the fluid that surrounds the brain. And then it has to get from that fluid into the blood. bloodstream to get to the kidney and livers.

Oh, it's, I mean, this pump then is like a pressure difference between those fluids. This pump is them actually using ions on individual cells to pull the water molecules along and out of the brain. So it isn't a pressure difference. It's literally like... It's an ionic pump. I mean, that's what cells do, right? They pump ions. And so you can use those ions to move fluid, including water through the brain. And it appears that's what's happening. Oh, wow. Okay. This sounds really interesting because it sounds like you can, like, generate these slow electric waves.

And you can kind of switch on this dishwasher. Exactly. And that brings us to the second paper in nature. It came from a team led by Liwe Tsai, who directs the Peekauer Institute for Learning and Memory at MIT. For several years, she's been working on a way to generate slow waves, you know, these things that are called gamma waves, without using any invasive technique, you know, like, putting electrical probes into the brain. And I spoke with her several years ago when she had just published a paper showing

that she could do this in mice. Wow. We can actually boost gamma waves by simply showing mice, 40 hertz flickering light, and playing a 40 hertz buzzing sound. This increases the power and synchrony of gamma waves tremendously.

Wow. Okay, so 40 hertz. We're talking about like cycles per second. 40 times a second. It's that simple. And with sound, for example, that frequency produces a kind of low tone. But in fact, the experiments have used 40 hertz clicks. So 40 clicks a second. And that sounds kind of like this. Huh. So that's all it takes to make gamma waves in my brain. And it starts to clear out my toxins. Well, you might also need some flickering light, which they also use. used in the experiments. Okay. But, you know, the paper that came out in early 2024 showed that when mice got this kind of sensory stimulation, their brains not only produced more gamma ways, they also switched

on that dishwasher and began clearing out amyloid, you know, one of the toxins associated with Alzheimer's. But the bottom line is, like, humans aren't mice, right? Will this light and sound actually help people not get Alzheimer's? That is not clear yet. And it's not clear, for instance, how many minutes have stimmer. Right. Right.

Right. Or precisely what kind of stimulation. But this type of sensory stimulation, 40 Hertz, seems to boost gamma waves in people. And the MIT folks, I should say, have already patented a device that delivers this sort of sensory stimulation to people. Really? They're already on top of it. Okay.

So you're going to come back and tell us like what's going to happen, right? When I know something, Gina, you will too. Excellent. Thank you so much for bringing us this story. This has been great. Always a pleasure. It makes brainwashing good. So good.

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That's plus.npr.org. Thank you. This episode was produced by Burley McCoy, edited by a showrunner Rebecca Ramirez, and fact-checked by John. And it was engineered by Maggie Luthor. Bet Donovan is our senior director and Colin Campbell is our senior vice president of podcasting strategy. I'm Regina Barber. Thank you for listening to Shortwave from NPR.