The incredible science of the sleeping brain

Summary

Science Weekly: "The Incredible Science of the Sleeping Brain"

The Guardian, June 2, 2026
Host: Ian Sample
Guest: Professor Maiken Nedergaard, Neuroscientist (University of Rochester Medical School & University of Copenhagen)

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Episode Overview

This episode dives into the cutting-edge science of why we sleep—focusing on the glymphatic system, the brain’s unique way of cleaning itself during sleep. Host Ian Sample and guest Professor Maiken Nedergaard explore discoveries on how this process is connected to brain health, neurodegeneration, and the influence of neurotransmitters, offering listeners practical insights into why sleep isn’t just about rest, but essential maintenance for our brains.

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Key Discussion Points and Insights

1. Why Do We Sleep?

• Sleep is a fundamental mystery in biology; its purpose has long been debated.
  • Quote: "Sleep is still one of the biggest mystery in biology and we still do not know why it is so important to sleep." — Professor Maiken Nedergaard [00:33]
• Sleep places animals, including humans, in a vulnerable state, yet it’s essential for life and performance.
  • Quote: "It puts us in such a vulnerable state and yet it's vital to life for almost all animals." — Ian Sample [00:41]

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2. Not Just Restoration and Memory: Housekeeping Takes Center Stage

• Early theories focused on rest, recovery, and memory consolidation.
• Nedergaard’s research shows sleep is crucial for "housekeeping" functions, especially for brain health:
  • Immune activity
  • Clearing metabolic and protein waste (e.g., amyloid, tau)
  • Quote: "We now realize that sleep is so much more than that...many housekeeping functions...it's not all about memory performance." — Professor Maiken Nedergaard [01:14]

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3. The Glymphatic System: How the Brain Cleans Itself

• Nedergaard’s lab discovered the glymphatic system (2012), revealing that the brain flushes out waste via cerebrospinal fluid (CSF) channels—primarily during sleep.
  • Quote: "The brain appears to only be able to do the basic housekeeping when we asleep." — Professor Maiken Nedergaard [02:27]
• The process:
  • During sleep, CSF flows into the brain, picking up waste products and carrying them away.
  • This process is mostly inactive when we are awake.
  • Quote: "If we injected colored substances in the cerebrospinal fluid ... and the animal was asleep, were pumped straight back into the brain ... when we started to do awake mice, we saw, wow, it doesn't happen." — Professor Maiken Nedergaard [03:05]
• The glymphatic system has since been confirmed in humans.
  • Activation occurs mostly during sleep, follows specific fluid patterns. [03:58–04:25]

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4. Link to Neurodegenerative Disease and Age

• Over 3,000 research papers on the glymphatic system highlight its importance in:
  • Alzheimer's, Parkinson's, frontotemporal dementia, and more.
  • Quote: "It is significant, handily reduced in all neurodegenerative diseases...aging in itself would decrease it." — Professor Maiken Nedergaard [04:37]
• Sleep deprivation rapidly impacts this system.
  • Quote: "If you keep awake for just one night, it takes at least two days or more to clean out the waste..." [04:37]

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5. Role of Neurotransmitters: More Than Mood and Cognition

• Neurotransmitters like noradrenaline, dopamine, and serotonin drive our waking selves (emotion, cognition, desire). [05:40]
• During sleep:
  • These neurotransmitters synchronize into slow waves (once per minute), driving fluid flow in the brain.
  • This synchronization is key for glymphatic function—ties evolutionary biology with sleep dynamics.
  • Quote: "They all synchronize activity and they oscillate, so they increase about once every minute and fall so very, very slow oscillations." — Professor Maiken Nedergaard [06:16]
• When awake, neurotransmitter activity is scattered, so fluid movement—and thus cleaning—does not happen. [07:27]

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6. Consequences of Disruption: Age, Stress, and Mental Illness

• Aging stiffens blood vessels, reducing their movement, making cleaning less efficient—linked to neurodegenerative disease. [09:12]
• Chronic stress and various mental illnesses (e.g., depression, schizophrenia):
  • Disrupt normal neurotransmitter cycles, impacting both wakefulness and sleep.
  • This disruption leads to inefficient cleaning and increased dementia risk.
  • Quote: "If noradrenaline signaling is messed up when we are awake, it certainly also messed up when we are asleep. And therefore the cleaning is not as efficient as it should be." — Professor Maiken Nedergaard [09:12]

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7. The Sleep–Dementia Link: Cause, Effect, and Opportunities

• Correlation between mental illness, poor sleep, and higher dementia risk is now being understood through glymphatic disruption.
  • Quote: "If you suffer from depression, schizophrenia, you are chronic stressed, you have an increased risk of premature dementia." — Professor Maiken Nedergaard [10:43]
• Early dementia may start with dysfunction in nerve cells producing neurotransmitters—a "chicken and egg" relationship between sleep disruption and disease onset.
  • Quote: "The first nerve cells that are affected...are the nerve cells that are producing the neurotransmitters...so it is a chicken and the egg." — Professor Maiken Nedergaard [12:03]
• This knowledge could accelerate novel drug developments and treatments for delaying dementia.

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8. Future Implications: Measuring and Improving Sleep Quality

• Potential for practical tools: heart rate variability (HRV) measured by smart devices could act as a sleep quality biomarker, reflecting glymphatic activity.
  • Quote: "You can use heart rate variability as a biomarker of the quality of sleep." — Professor Maiken Nedergaard [12:50]

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9. Top Takeaways and Sleep Advice for Listeners

• Sleep isn’t passive rest; it’s an "active housekeeping" vital for long-term brain health and healthy aging.
• Prioritize consistent, restful sleep—not obsessively tracking metrics, but focusing on feeling refreshed.
  • Quote: "All of these sleep devices that's monitoring sleep is probably not the way to go because it makes sleep a competition... What it's about is that you wake up in the morning, you feel refreshed and capable of embarking in a happy way on the day." — Professor Maiken Nedergaard [13:45]
• If at risk for neurodegeneration: building healthy sleep routines should be a priority.

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Notable Quotes & Memorable Moments

• "Sleep is still one of the biggest mystery in biology and we still do not know why it is so important to sleep."
  — Professor Maiken Nedergaard [00:33]

• "If we injected colored substances in the cerebrospinal fluid ... when the animal was asleep, we were pumped straight back into the brain ... when we started to do awake mice, we saw, wow, it doesn't happen."
  — Professor Maiken Nedergaard [03:05]

• "If you keep awake for just one night, it takes at least two days or more to clean out the waste..."
  — Professor Maiken Nedergaard [04:37]

• "They all synchronize activity and they oscillate, so they increase about once every minute and fall so very, very slow oscillations."
  — Professor Maiken Nedergaard on neurotransmitters during sleep [06:16]

• "If noradrenaline signaling is messed up when we are awake, it certainly also messed up when we are asleep. And therefore the cleaning is not as efficient as it should be."
  — Professor Maiken Nedergaard [09:12]

• "All of these sleep devices that's monitoring sleep is probably not the way to go because it makes sleep a competition... What it's about is that you wake up in the morning, you feel refreshed and capable of embarking in a happy way on the day."
  — Professor Maiken Nedergaard [13:45]

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Timestamps for Important Segments

• 00:27-01:14 – Opening discussion: Why do we sleep?
• 02:27-03:39 – Discovery of glymphatic system and its unique sleep-dependency
• 04:25-05:21 – Glymphatic impact and links to neurodegeneration, aging, and sleep deprivation
• 05:40-06:56 – Neurotransmitters’ shifting roles between wake and sleep
• 07:27-09:12 – How synchronized neurotransmitter waves drive brain cleaning during sleep
• 09:12-11:47 – Disruption via age, stress, mental illness, and link to dementia
• 12:03-12:29 – How glymphatic research is opening doors to treatments
• 12:50-end – HRV and practical sleep advice

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Practical Listener Takeaways

• Prioritize regular, high-quality sleep for long-term brain health; it’s fundamental to cleaning out the waste that accumulates in a busy brain.
• Don't obsess over tracking sleep metrics. Instead, focus on how you feel after sleep—a refreshed morning is a sign your brain has done its housekeeping.
• Recognize signs of chronic sleep disruption as potential early warning for neurodegenerative risk, especially if coupled with stress or mental illness.

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For more on the glymphatic system and latest sleep science, explore research by Professor Maiken Nedergaard and keep an eye on developments in smart health tech for sleep quality.

Transcript

[Guardian Advertiser]

This is the Guardian. Summer smells like citrus in the sun. Turn your home into a daily getaway with Pura's new summer collection. Find your flow and fragrance and explore the [e-mail].

[Ian Sample]

For thousands of years, humans have pondered the question, why do we sleep?

[Professor Maiken Nedergaard]

Sleep is still one of the biggest mystery in biology and we still do not know why it is so important to sleep.

[Ian Sample]

It puts us in such a vulnerable state and yet it's vital to life for almost all animals.

[Professor Maiken Nedergaard]

I think we all feel on our body on a daily level how much sleep actually matter for our performance and our well being the following day.

[Ian Sample]

Hypotheses about sleep's purpose have changed as we learn more from rest and recovery for the body to consolidating memory in the brain. But according to neuroscientist Mike and Nedergaard, it goes even further.

[Professor Maiken Nedergaard]

We now realize that sleep is so much more than that and that probably many both immune action, many housekeeping functions that's going on in sleep. And it's not all about memory performance.

[Ian Sample]

As we understand more about the biology of sleep, its importance is becoming clearer. And it turns out that sleep disruption could have major consequences for our future brain health. So today, the incredible science of the sleeping brain and why it all comes down to good housekeeping. From the Guardian. I'm Ian Samble and this is Science Weekly. Micah Nedergaard, you're professor of neuroscience at Rochester Medical School and at the University of Copenhagen. And back in 2012, your lab was behind the groundbreaking discovery of this mechanism the brain has for clearing out its waste, which you named the glymphatic system. So first of all, what does this cleaning system have to do with sleep?

[Professor Maiken Nedergaard]

All other organ and tissue can do the housekeeping, the cleaning when we asleep, when we're awake, at any time point, the brain appears to only be able to do the basic housekeeping when we asleep.

[Ian Sample]

Right. So unlike every other organ, the brain can only clean out its waste molecules, proteins like amyloid and tau and metabolic byproducts while we're sleeping, which provides a clue as to what sleep might be for. And this process all centers on what's happening to the fluid that surrounds the brain, the cerebrospinal fluid. How did you discover this mechanism?

[Professor Maiken Nedergaard]

Yeah, what we found in a nutshell was that if we injected colored substances in the cerebrospinal fluid that surround the brain, we found that if the animal was asleep, were pumped straight back into the brain. And this was very unexpected finding because the cerebrospinal fluid is Supposed to be basically produced by the brain and then protect the brain and leave the brain. And then when we started to do awake mice, we saw, wow, it doesn't happen. So, of course, we mistrusted it, we repeated it many times, used different technique, and we published it.

[Ian Sample]

And so this was your big discovery, the glymphatic system, essentially these channels running alongside blood vessels in the brain, which cerebrospinal fluid can flow through and flush out any waste. But has it actually been observed in the living human brain?

[Professor Maiken Nedergaard]

Yes. So that is a big deal. So all the basic concept of the glymphatic system was defined in mice and rats. But very quickly, just a few years later, people start to replicate these findings and could confirm the core principle of the glymphatic system. For example, that it turns on when we sleep, it turns off when we awake, and it follows a certain pattern or organization of fluid flow.

[Ian Sample]

So you and other scientists have pieced together what is going on with the glymphatic system, what it seems to be doing and how it seems to be working. Tell me what the impact of this discovery has been.

[Professor Maiken Nedergaard]

Yeah. There has been about 3,000 papers published on the glymphatic system. And what people have done so far is to describe the drivers of it, that it is significant, handily reduced in all neurodegenerative diseases. So this is Alzheimer, Parkinson, frontotemporal dementia, and so on. It's decreased, and aging in itself would decrease it. It's also been shown that it's suppressed by wakefulness. And if you keep awake for just one night, it takes at least two days or more to clean out the waste that accumulated during that night. Foreign.

[Ian Sample]

Over the past five years or so, we've seen further advances in understanding how this system operates, and particularly the role of neurotransmitters in the operation of the glymphatic system. Can you tell me what the neurotransmitters are doing in our bodies during the day, in our waking hours?

[Professor Maiken Nedergaard]

Yes. So the neurotransmitters are modulators. So these are noradrenaline, dopamine, serotonin. They are basically determining when we awake, who we are, because they're driving emotion, cognition, and desire. So they have very different functions. Sometimes they work in parallel, but most of the time they work in different brain region and a different time point.

[Ian Sample]

Okay. So when we're awake, these neurotransmitters, like dopamine and serotonin are acting individually, but now we understand that they're doing something surprising when we're asleep. What's that?

[Professor Maiken Nedergaard]

So the biggest surprise was that they all synchronize activity and they oscillate, so they increase about once every minute and fall so very, very slow oscillations. What it comes down to is that during evolution, the brain probably decided to use the neurotransmitters for two different purposes. One to decide our awake desire and cognition, and the other is these are the driver of fluid flow when we fall asleep. So this is very common in evolution, that the same building block is used for multiple purposes, often to a tree.

[Ian Sample]

So what you're saying is we have these chemical messengers that have their specific individual roles in how we feel, how we behave when we're awake. But they have this other role when we're sleeping, which is tied into the glymphatic system, which is tied into how our brain is clearing out some of this metabolic waste that we've been talking about. The changes you were talking about, what are they doing in the brain and body while we're sleeping? What is the consequence of these sort of slow waves of activity?

[Professor Maiken Nedergaard]

Yeah, so this slow wave of activity actually appeared in evolution about 600 million years ago when the very primitive organism started to have a gut and a vascular system, and you need to move fluid about in these systems. This organism did not even have a heart, but they still have very simple vessels that could move oxygen from one place to another by this very slow oscillation. And what probably happened is that evolution decided this is actually a great function to basically constrict and dilate blood vessels about once every minute, and that is maintained in the human brain. Now, we know this is what moves fluid around when we sleep, and we also know why it doesn't happen when we are awake. Because these neurotransmitters are not synchronized. They move a little here, a little there, so there's no concerted movement of fluid flow. When they all synchronize. When we sleep, we get this highly organized movement of not only blood, but also cerebral spinal fluid, and that is what drives brain clearance.

[Ian Sample]

So when we're sleeping, and specifically it's during non REM sleep, we fall into this state where the release of these neurotransmitters, these chemicals like serotonin, dopamine, norepinephrine, they're synchronized into slow waves. And that seems to be driving this kind of pump that moves the cerebrospinal fluid through the brain. And as it moves through the brain, it's sort of picking up the waste that is accumulating in the brain. That's how it all works in a healthy situation. And then there are things that can disrupt that.

[Professor Maiken Nedergaard]

So there's many things that can disrupt it. As the brain age, the blood vessel gets stiffer, they do not move as much, and therefore cleaning is not efficient any longer. And that is probably one of the reasons we accumulate proteins and we get Alzheimer's and Parkinson's disease and so on. But the new discovery that these neurotransmitters are such a key for driving this cleaning process open up for the question. If you are mentally sick or you are chronic stressed during daytime, you know that the signaling for noradrenaline is not functioning normal. And if noradrenaline signaling is messed up when we are awake, it certainly also messed up when we are asleep. And therefore the cleaning is not as efficient as it should be.

[Ian Sample]

Coming up, how the quality of your sleep today can impact your brain's health in the future. Mike, and you mentioned that age, chronic stress, and some mental illnesses can disrupt this really important weight clearance system. But we also know that there's a connection between these conditions and our risk of dementia. And I'm really interested in what the link is there, why and how might these be related?

[Professor Maiken Nedergaard]

So it's very well documented in many, many studies that if you suffer from depression, schizophrenia, you are chronic stressed, you have an increased risk of premature dementia. And that has not been possible to really define why that happened earlier. And I think with the dual funct of these neurotransmitters, we have an answer. We know that the neurotransmitters basically disturb the signaling during wakefulness, and it remains to be shown that it's disturbed during sleep and therefore glymphatic clearance is reduced. But we already know that all of these diseases are associated with very significant sleep disorders. And that in itself would very significantly reduce glymphatic flow, because glymphatic flow need healthy long term sleep. Short, fragmented sleep is basically returning some of the waste to the brain. So having normal sleep, normal neurotransmitter oscillation is probably the key to restorative sleep.

[Ian Sample]

Okay, so I can see how poor sleep could make it harder for our brains to clear out waste and how that could potentially drive dementia. But might there not be more to it? Maybe these problems with sleep are themselves early signs of dementia.

[Professor Maiken Nedergaard]

Yeah, that is completely right. The first nerve cells that are affected in patients that are developing dementia are the nerve cells that are producing the neurotransmitters so it is a chicken and the egg, but we can use this new knowledge to basically test new treatments and that would greatly accelerate drug development to delay dementia.

[Ian Sample]

And I think that is really interesting because I was wondering that given the richness of the understanding of this glymphatic system that scientists like yourself are now really getting, whether there are realistic clinical applications, and it sounds like you're saying there are ways to put the knowledge we know now already to good use potentially to help some of these patients.

[Professor Maiken Nedergaard]

Yeah. So the benefit of this new discovery is that we can go in and measure probably something as simple as heart rate variability with a smartwatch and basically follow not only how long do you sleep, how much REM sleep do you have, but actually measure the quality of sleep. It's not been proven yet. It's fairly logic that since the neurotransmitters are regulating both brain clearance and heart rate variability, you can use heart rate variability as a biomarker of the quality of sleep.

[Ian Sample]

So finally, Mike, and clearly deep sleep is not this quiet, inactive state of rest that some of us might have thought it was. But I'm wondering what our listeners should take away from this work. We've been talking about how they should be thinking about their own approach to sleep.

[Professor Maiken Nedergaard]

Yes, sleep is a serious process that one should consider for aiming for healthy aging. So really consider building it in. In your daily life, you basically arrange your day around that you have both a rich day where you feel satisfied and you go home and you keep your sleep time. Something as basic as that, if you're at risk for developing Alzheimer's disease is probably something that could be done. But I also think that all of these sleep devices that's monitoring sleep is probably not the way to go because it makes sleep a competition. Do you really sleep well enough? How was my sleep? And that's not really what it's about. What it's about is that you wake up in the morning, you feel refreshed and capable of embarking in a happy way on the day.

[Ian Sample]

Thanks to Professor Michaen Nadergaard. And that's all from us. This episode was produced by Ellie Sands. The sound design was by Ross Burns and the executive producer was Ellie Burey. We'll be back on Thursday. See you then.

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