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

This episode explores how the brain eliminates its waste, particularly focusing on a system akin to the lymphatic system, termed the glymphatic system, which operates predominantly during sleep.

1. The brain disposes of waste using a special system called the glymphatic system, which is most active during sleep.
2. Disrupted sleep can prevent this system from functioning properly, leading to the accumulation of brain toxins like amyloid beta and tau proteins.
3. Recent research shows a potential link between the quality of sleep and the likelihood of developing neurological diseases like Alzheimer's.
4. Innovative studies suggest that inducing slow electrical brain waves might enhance the glymphatic system's activity.
5. Non-invasive methods like flickering lights and sounds could potentially stimulate this cleaning process in humans.

1: Introduction to Brain Waste

Overview of the types of waste the brain needs to clear, including toxic proteins involved in Alzheimer's. Discussion on how these accumulations impact brain function. Regina Barber: "So what kind of waste does the brain need to get rid of?" John Hamilton: "Cells need to clear away toxic proteins like beta amyloid."

2: The Glymphatic System

Explanation of the glymphatic system discovered in 2012, likened to a brain's "dishwasher," which intensively operates during sleep to clean the brain. John Hamilton: "During deep sleep, the brain's glymphatic system works like a dishwasher, washing away waste."

3: Implications of Sleep Disruption

Details on studies showing how sleep disruption affects the glymphatic system's efficiency and the potential long-term consequences for brain health. John Hamilton: "Interrupted deep sleep reduces the effectiveness of the brain's cleaning process, increasing toxin levels."

1. Prioritize getting quality deep sleep to support your brain's natural cleaning processes.
2. Consider using sleep aids like white noise or blackout curtains to improve sleep quality.
3. Engage in regular physical activity, which can promote better sleep and, in turn, better brain health.
4. Avoid stimulants like caffeine close to bedtime to prevent sleep disruption.
5. Create a consistent bedtime routine to help signal your body it's time to sleep and potentially enhance deep sleep phases.

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.

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Maiken Nedergaard, Laura Lewis, John Hamilton, Regina Barber

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Regina Barber
You're listening to short wave from NPR.

Hey, short waivers. Regina Barber 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.

John Hamilton
Hey, Gina.

Regina Barber
So what kind of waste does the brain need to get rid of?

John Hamilton
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.

Regina Barber
Maybe that disease is coming from all that garbage kind of getting built up in your brain.

John Hamilton
That is the idea. That is what most scientists believe right now.

Regina Barber
How does stuff build up in the brain?

John Hamilton
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 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 your 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.

Regina Barber
Oof. That's not good. So how does, like, my brain, your brain? Our brains clean themselves.

John Hamilton
That really wasn't clear until about 2012, 2013.

That was when a team led by a danish scientist named Micah Nedergaard 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.

Maiken Nedergaard
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.

Regina Barber
That's so cool. I love the visual, right?

John Hamilton
And so for the past decade, scientists 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.

Regina Barber
So today on the show, how brain washing helps keep diseases away and why.

John Hamilton
This sound might start the washing process.

Regina Barber
You're listening to shortwave, the science podcast from NPR.

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Regina Barber
Ok, so were talking about how the brain gets rid of waste. Is that different than what happens in the rest of the body?

John Hamilton
It is. The body has something called the lymphatic system. Its 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 into the bloodstream. And ultimately 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 that is a mashup of glia, a kind of brain cell that's central to the process. And lymphatic glia. Lymphatic glymphatic.

Regina Barber
I love it. So, scientists find this dishwasher in the brain. What happens next?

John Hamilton
One thing they needed to figure out whether the glymphatic 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.

Regina Barber
Yeah. How did they go about studying that in mice?

John Hamilton
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 brains started accumulating these toxic proteins that are associated with Alzheimer's. Wow.

Regina Barber
Okay.

John Hamilton
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 brains 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.

Regina Barber
Oh, my God, that's so mean.

John Hamilton
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.

Regina Barber
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 therapy?

John Hamilton
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 Peakower Institute at MIT.

What Laura's team did was find a way to watch the entire process happen in the brains of eleven people as they slept. She told me that when people entered deep sleep, these slow electrical waves would start appearing in the brain.

Laura Lewis
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 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.

Regina Barber
What was the fluid like? Walk me through what she just said.

John Hamilton
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. Other research has shown. And then there's this rush of fluid into the brain. 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.

Jonathan Kipnis
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 did the other way around. We enhanced those waves, and now we saw more efficient clearance of that brain region.

Regina Barber
I'm still confused on what this fluid is.

John Hamilton
There are two kinds of fluid. There is what they call interstitial fluid, which is the fluid between the cells in the brain, between neurons.

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 bloodstream to get to the kidney and livers.

Regina Barber
Oh, it's. I mean, this pump then, is like a pressure difference between those fluids.

John Hamilton
This pump is them actually using ions on individual cells to pull the water molecules along and out of the brain.

Regina Barber
So it isn't a pressure difference.

John Hamilton
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 I to move fluid, including water, through the brain. And it appears that's what's happening.

Regina Barber
Oh, wow. Okay, this sounds really interesting because it sounds like you can generate these slow electric waves, and you can kind of switch on this dishwasher.

John Hamilton
Exactly. And that brings us to the second paper in nature. It came from a team led by Liwei Tsai, who directs the pkower 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.

Liwei Tsai
We can actually boost gamma waves by simply showing mice 40 hz flickering light and playing a 40 hz buzzing sound.

This increases the power and synchrony of gamma waves tremendously.

Regina Barber
Wow. Okay, so 40 hz, we're talking about, like, cycles per second, 40 times a second.

John Hamilton
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 hz clicks. So 40 clicks a second. And that sounds kind of like this.

Regina Barber
Huh. So that's all it takes to make gamma waves in my brain, and it starts to clear out my toxins?

John Hamilton
Well, you might also need some flickering light, which they also used in the experiments.

Regina Barber
Okay.

John Hamilton
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 waves, they also switched on that dishwasher and began clearing out amyloid, you know, one of the toxins associated with Alzheimer's.

Regina Barber
But the bottom line is, like, humans aren't mice, right? Will this light and sound actually help people not get Alzheimer's?

John Hamilton
That is not clear yet. And it's not clear, for instance, how many minutes of stimulation you need each day or precisely what kind of stimulation. But this type of sensory stimulation, 40 hz, 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.

Regina Barber
Really? They're already on top of it. Okay, so you're gonna come back and tell us, like, what's gonna happen, right?

John Hamilton
When I know something, Gina, you will too.

Regina Barber
Excellent. Thank you so much for bringing us the story. This has been great.

John Hamilton
Always a pleasure.

Regina Barber
It makes brainwashing good.

John Hamilton
So good.

Regina Barber
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This episode was produced by Burleigh McCoy, edited by our showrunner Rebecca Ramirez, and fact checked by John. And it was engineered by Maggie Luthar. Bette Donovan is our senior director and Colin Campbell is our senior vice president of podcasting strategy. I'm Regina Barbour. Thank you for listening to short wave from NPR.

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