Deep sleep doesn’t just rejuvenate your body — it clears your mind by flushing out waste that builds up during waking hours.
Scientists discovered that norepinephrine, released in rhythmic waves during deep sleep, drives the brain’s glymphatic system, which pumps cerebrospinal fluid to clear toxins. However, sleep aids like zolpidem may disrupt this process, reducing the brain’s cleaning efficiency.
Understanding the Brain’s Waste Removal System
Getting a good night’s sleep does more than leave you feeling refreshed — it actively clears your brain. New research, published on January 8 in the journal Cell, reveals that deep sleep helps flush out waste that builds up in the brain during waking hours. This natural cleansing process is vital for maintaining brain health. The study also highlights how sleep aids might interfere with this “brainwashing” mechanism, potentially impacting long-term cognitive function.
The brain relies on a built-in waste removal system called the glymphatic system, which circulates fluid throughout the brain and spinal cord to eliminate waste. This system helps clear away toxic proteins that can accumulate and form sticky plaques, a hallmark of neurological disorders. However, the mechanisms driving this system had remained unclear — until now.
The Role of Norepinephrine in Brain Cleaning
Researchers in Denmark discovered that a molecule called norepinephrine plays a crucial role in this process, at least in mice. During deep sleep, the brainstem releases tiny waves of norepinephrine roughly every 50 seconds. These waves cause blood vessels in the brain to contract, creating slow, rhythmic pulsations that propel surrounding fluid to carry away waste effectively.
“It’s like turning on the dishwasher before you go to bed and waking up with a clean brain,” says senior author Maiken Nedergaard of the University of Rochester and University of Copenhagen, Denmark. “We’re essentially asking what drives this process and trying to define restorative sleep based on glymphatic clearance.”
How Norepinephrine Drives Fluid Flow
To find clues, Nedergaard and her team looked into what happens in mice when the brain sleeps. Specifically, they focused on the relationship between norepinephrine and blood flow during deep slumber. They found that norepinephrine waves correlate to variations in brain blood volume, suggesting norepinephrine triggers a rhythmic pulsation in the blood vessels.
Blood Vessels as Brain Fluid Pumps
The team then compared the changes in blood volume to brain fluid flow. They found that the brain fluid flow fluctuates in correspondence to blood volume changes, suggesting that the vessels act as pumps to propel the surrounding brain fluid to flush out waste.
“You can view norepinephrine as this conductor of an orchestra,” says lead author Natalie Hauglund of the University of Copenhagen and the University of Oxford, UK. “There’s a harmony in the constriction and dilation of the arteries, which then drives the cerebrospinal fluid through the brain to remove the waste products.”
Does All Sleep Promote Brain Health?
Hauglund then had another question — is all sleep created equal? To find out, the researchers gave mice zolpidem, a common drug to aid sleep. They found that the norepinephrine waves during deep sleep was 50% lower in zolpidem-treated mice than in naturally sleeping mice. Although the zolpidem-treated mice fell asleep faster, fluid transport into the brain dropped more than 30%. The findings suggest that the sleeping aid may disrupt the norepinephrine-driven waste clearance during sleep.
“More and more people are using sleep medication, and it’s really important to know if that’s healthy sleep,” says Hauglund. “If people aren’t getting the full benefits of sleep, they should be aware of that so they can make informed decisions.”
Human Implications of Sleep Research
The team says that the findings likely apply to humans, who also have a glymphatic system, although this needs further testing. Researchers have observed similar norepinephrine waves, blood flow patterns, and brain fluid flux in humans. Their findings may offer insights into how poor sleep may contribute to neurological disorders like Alzheimer’s disease.
“Now we know norepinephrine is driving the cleaning of the brain, we may figure out how to get people a long and restorative sleep,” says Nedergaard.
For more on this study, see How Zolpidem May Damage Your Brain’s Cleanup System.
Reference: “Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep” by Natalie L. Hauglund, Mie Andersen, Klaudia Tokarska, Tessa Radovanovic, Celia Kjaerby, Frederikke L. Sørensen, Zuzanna Bojarowska, Verena Untiet, Sheyla B. Ballestero, Mie G. Kolmos, Pia Weikop, Hajime Hirase and Maiken Nedergaard, 8 January 2025, Cell.
DOI: 10.1016/j.cell.2024.11.027
This work was supported by the Lundbeck Foundation, the Novo Nordisk Foundation, the National Institutes of Health, the US Army Research Office, the Human Frontier Science Program, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the Simons Foundation, the Cure Alzheimer Fund, the Danmarks Frie Forskningsfond, and JPND/Good Vibes.
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1 Comment
The lymphatic system, which drains everything downwards from the head, runs along and in the throat and neck area.
Manual lymphatic drainage could be used to test the extent to which the glymphatic system in the brain can be influenced.
From earlier writings, from one of the first books on manual lymphatic drainage by “Földi” it is written…. That fluids were already found in the throat and neck area that could only come from the brain area. But I didn’t know exactly how it got there. My lymphatic drainage teacher at the time told me that the system simply looks for the nearest lymph vessels that can drain it. This can also be a path through the connective tissue to the nearest lymph vessels or lymph nodes.
However, it would be interesting to investigate the extent to which a therapist can influence the glymphatic system with manual lymphatic drainage by increasing the suction effect.