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A restful night does much more than rejuvenate your body—it might actually refresh your brain. A recent study published on January 8 in the Cell Press journal Cell illustrates how deep sleep may help eliminate waste accumulated in the brain while we are awake, a crucial process for sustaining brain health. The research also sheds light on how sleep medications could interfere with this ‘brain-cleaning’ mechanism, which may have long-term effects on cognitive abilities.
Researchers have discovered that the brain features a natural waste elimination system known as the glymphatic system. This system circulates fluid throughout the brain and spinal cord to remove waste, helping to eliminate toxic proteins that lead to sticky plaques associated with neurological conditions. However, the driving mechanisms behind this system were previously not well understood, until now.
Scientists from Denmark have identified that a molecule called norepinephrine is crucial for the brain’s cleaning process in mice. During deep sleep, the brainstem releases small waves of norepinephrine roughly every 50 seconds. This molecule causes blood vessels to constrict, creating slow pulsations that facilitate a rhythmic flow in the surrounding fluid to carry waste away.
“It’s like activating the dishwasher before going to sleep and waking up to a spotless brain,” explains Maiken Nedergaard, the study’s senior author from the University of Rochester and University of Copenhagen, Denmark. “We’re asking what initiates this process and attempting to define restorative sleep in terms of glymphatic clearance.”
To uncover more details, Nedergaard and her colleagues examined what transpires in the brains of sleeping mice. They specifically studied how norepinephrine and blood flow interact during deep sleep. Their findings indicated that norepinephrine waves aligned with fluctuations in brain blood volume, implying that norepinephrine initiates rhythmic pulsations in the blood vessels.
Next, the researchers compared the changes in blood volume to the flow of brain fluid. They found that the movement of brain fluid fluctuated in tandem with changes in blood volume, suggesting that the vessels act as pumps that help propel the surrounding fluid to cleanse the brain of waste.
“You can think of norepinephrine as the conductor of an orchestra,” says Natalie Hauglund, the lead author from the University of Copenhagen and the University of Oxford, UK. “There’s a synchronization in the constriction and dilation of arteries, which then drives cerebrospinal fluid through the brain, helping to remove waste products.”
Hauglund had another inquiry—are all sleep types equally beneficial? To investigate this, the team administered zolpidem, a common sleeping aid, to mice. They discovered that the norepinephrine waves during deep sleep were 50% lower in mice treated with zolpidem compared to those sleeping naturally. Although the zolpidem-treated mice fell asleep more quickly, there was over a 30% decrease in fluid transport into the brain. These results indicate that the sleeping aid may disrupt norepinephrine-driven waste clearance during slumber.
“With an increasing number of people relying on sleep medications, it is vital to understand whether this leads to healthy sleep,” says Hauglund. “If individuals are not reaping the full benefits of sleep, they should be informed so they can make educated choices.”
The research team suggests that these findings are likely applicable to humans, who also possess a glymphatic system, although further investigations are necessary. Similar norepinephrine waves, blood flow patterns, and brain fluid movements have been observed in humans. The implications of their findings may enhance our understanding of how inadequate sleep could contribute to neurological disorders like Alzheimer’s disease.
“Now that we know norepinephrine is pivotal for brain cleansing, we might be able to develop ways for individuals to achieve prolonged and restorative sleep,” concludes Nedergaard.
This study was funded 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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