Scientists Discover Another Reason Sleep is Important
Our neurons and brainwaves keep our brains clean of waste
Hiya!
Sleep has always mystified us. We’ve long pondered questions about why we dream, what they mean, what our brain does while we sleep, and why we sleep at all. I don’t know if we’ll ever learn everything there is to know about sleep, but the scientific community has learned a surprising amount over recent decades, with more discoveries made every year.
For instance, we now know that our brains are anything but dormant when we sleep. Instead, as our bodies are inactive, our brain cells create bursts of electrical pulses that generate rhythmic waves that sweep the brain. But why are our brains so active when we’re supposed to be resting? Scientists have identified a few reasons, like that we process information and emotions as we doze, but now scientists have discovered another vital function the brain performs while we sleep.
Waste in the Brain
Like other highly complex organisms, humans have billions of neurons in the functional tissue of our brains, which is protected by the blood-brain barrier. Functional tissue, called parenchyma, is tissue with cells that serve a “function,” such as storing information in a brain or photosynthesis in plants. These cells differ from those in “structural” tissues, which are cells that form things like bone in animals or wood for trees.
Like everything else in Life, neurons require energy to function. They get energy from the nutrients we consume and use it to complete complex tasks like committing our experiences to memory and problem-solving. Except neurons aren’t very efficient eaters; they’re more like the Cookie Monster on Sesame Street, spitting crumbs as he gobbles cookies.
The debris, or crumbs, left behind after neurons consume nutrients is called metabolic waste, which mainly consists of protein fragments. Some research suggests that an accumulation of these fragments may play a role in neurodegenerative diseases like Alzheimer’s.
For a while, scientists thought each cell took care of its own metabolic waste, like cleaning our dishes after we eat. The idea was that as cells age, they become less efficient at clearing their waste, which could hypothetically cause a build-up of metabolic waste that contributes to neurodegenerative diseases.
Then, in 2013, Danish neuroscientist Maiken Nedergaard discovered the glymphatic system (which is different from our lymphatic system.) The glymphatic system carries cerebrospinal fluid through the brain via channels near blood vessels, filtering debris out of the brain’s functional tissues in the process.
More specifically, cerebrospinal fluid enters the brain and collects toxic waste as it weaves through complex cellular webs. After exiting the brain, the contaminated fluid passes through a barrier and is dumped into lymphatic vessels in the outer tissue layer between the brain and skull, called the dura mater.
As exciting as Nedergaard’s research was, it inspired the same question that arises after every discovery: What came before? In this case, if the glymphatic system is responsible for clearing debris from our brain, what instructs or powers the system to do it?
Just over a decade later, researchers at the Washington University School of Medicine in St. Louis (WUSTL) might have an answer.
The Study
In February 2024, scientists at WUSTL led by Jonathan Kipnis, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology & Immunology, and a BJC Investigator, published research in Nature suggesting rhythmic waves power the glymphatic system into action. In an article by Marta Wegorzewska of WUSTL’s The Source about the research, Kipnis explains:
“We knew that sleep is a time when the brain initiates a cleaning process to flush out waste and toxins it accumulates during wakefulness. But we didn’t know how that happens.”
To find out, Kipnis and his colleagues at WUSTL analyzed the brains of mice as they slept.
Part One
Once the mice fell asleep, neurons in their brains fired powerful electrical currents. Under anesthesia, the brain waves were mostly long and slow, which generated corresponding waves in the cerebrospinal fluid, which carried brain waste as it flowed through the dura mater.
Li-Feng Jiang-Xie, a postdoctoral research associate in the Department of Pathology & Immunology and the paper's first author, explained to Wegorzewska that neurons initiate the glymphatic system by coordinating their firing of electrical signals. This generates rhythmic waves that, in turn, propel fluid movement.
Part Two
To confirm their initial findings that neurons spark the glymphatic system into action, the researchers silenced specific brain regions in some mice so that neurons in those regions couldn’t create rhythmic waves.
They achieved this by genetically engineering the brains of some mice by implanting probes and inserting electrodes in the spaces between neurons. Then, the team anesthetized the mice with ketamine to significantly reduce neuronal activity as the engineered mice slept.
They also had mice that were untouched for comparison.
The Results
The team discovered that the long, slow brain waves they observed previously in the mice brains were now undetectable in the brains of the engineered mice. Without the waves, the fluid didn’t push or carry metabolic waste out of the brain. The researchers concluded this could only mean that the brain’s self-cleaning cycle depends on active neurons.
The scientists also noticed something intriguing in the brainwaves of the un-engineered mice. They weren’t always slow and steady but fluctuated, with some slightly faster waves occurring sporadically. The team hypothesizes that the faster waves may target stubborn debris that’s harder to remove — like scrubbing a dish harder where there’s extra crusted food residue.
Bonus Finding
Part of the reason it’s been over a decade since the breakthrough with the glymphatic system is that previous experiments produced different results. However, Kipsin and his team think their research can explain the lack of consistency in one word: anesthesia.
If their research is correct, and the glymphatic system relies on neural activity to flush cerebrospinal fluid through the brain, then the type of anesthetic used in previous studies matters. Some anesthetics inhibit neural activity, which could interfere with a study’s results.
Additionally, some older experiments used more invasive methods of implanting hardware into brain tissue, which likely injured the brain and could also disrupt neuron activity and the study’s results.
What’s Next?
There’s no shortage of ideas for what to do next, but the WUSTL researchers want to investigate the changes they observed in the mice’s brainwaves throughout sleep cycles. The team hopes to understand why neurons fire brainwaves in various rhythms during sleep and which brain regions are the most vulnerable to accumulated waste.
Plus, if neurons spur the glymphatic system into action, future research can focus on the intricacies of that process. Xie explained to Wegorzewska,
“These neurons are miniature pumps. Synchronized neural activity powers fluid flow and removal of debris from the brain. If we can build on this process, there is the possibility of delaying or even preventing neurological diseases, including Alzheimer’s and Parkinson’s disease, in which excess waste — such as metabolic waste and junk proteins — accumulate in the brain and lead to neurodegeneration.”
Learning more about the effects of accumulated metabolic waste and its removal could further our understanding of neurodegenerative diseases like Alzheimer’s and Parkinson’s that continue to confound experts.
Perspective Shift
So, not only is our brain busy processing our thoughts, emotions, and experiences from when we’re awake while we sleep, but it also undergoes a cleanse every night by sweeping cerebrospinal fluid through the brain to clean house and clear out the mess left behind by daytime activities. Wowzers. Nature is so cool.
I’ve always been a big fan of sleeping and try to prioritize it by sticking to a specific bedtime. It’s not always easy, especially if the show I’m watching is addictive, but I remind myself of the many benefits sleep provides, and now the WUSTL research adds another reason. Maybe this new knowledge will make it a little easier to turn off the TV at bedtime.
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Curious timing- I just recently read about the glymphatic system for the first time just a couple weeks ago, but this is much more detailed. Thank you so much for a deeply intriguing look into sleep patterns.
Very interesting. I’m going to bed early tonight!