How to Help Detox Your Brain by Understanding Your Glymphatic System

Ever wonder why you’re always reading about how important sleep quality is -- not just quantity?  Well, modern science still doesn’t know all of the molecular mechanisms behind why we need sleep. As of last month, we now know more.

A new study, published in Science in October and entitled “Sleep Drives Metabolite Clearance from the Adult Brain,” finds just that: we need to sleep specifically so that the brain can focus on cleaning itself out each night.

Lead study author Dr. Maiken Nedergaard summarizes in a statement: “the restorative nature of sleep appears to be the result of the active clearance of the by-products of neural activity that accumulate during wakefulness.”

The study’s abstract states:

We here report that sleep has a critical function in ensuring metabolic homeostasis. Using real-time assessments of tetramethylammonium diffusion and two-photon imaging in live mice, we show that natural sleep or anesthesia are associated with a 60% increase in the interstitial space, resulting in a striking increase in convective exchange of cerebrospinal fluid with interstitial fluid. In turn, convective fluxes of interstitial fluid increased the rate of ?-amyloid clearance during sleep. Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.

While you rest, your brain is busy sweeping the floor, washing the dishes, and taking out the trash to prepare itself for the next day.

Your Glymphatic System: The Good Kind of “Brain Drain”

You probably haven’t read much about the glymphatic system because it hasn’t hit the mainstream, but you will.

In 2012, researchers identified this new maintenance system called the glymphatic system, which uses the cells’ mitochondria to remove cellular waste from the brain. It found that the clear cerebrospinal fluid (CSF) in the brain is what is responsible for draining toxins from the brain, much like how the lymph system in other organs is what removes waste from those cells to the kidney and liver.  But the brain has no lymph – it has CSF instead.

The scientists noted that this system is particularly active during sleep. In other words, as you sleep your brain cells’ mitochondria remove cellular waste.

Things you can do during the waking hours that may positively influence the way cerebral spinal fluid (CSF) enters the brain’s glymphatic system later when you sleep:

Yoga and movement (especially inversions)

Standing instead of sitting at your desk which may move more CSF

Pranayama and just about any other breathing exercices

Massage and chiropractic care

Hydration

In the News: Lack Of Deep Sleep May Set The Stage For Alzheimer's

Jeffrey Iliff (right) and Bill Rooney, brain scientists at Oregon Health & Science University, look over an MRI. The school has an especially sensitive MRI unit that should be able to detect precisely when during sleep the brain is being cleansed of toxins.

There's growing evidence that a lack of sleep can leave the brain vulnerable to Alzheimer's disease.

"Changes in sleep habits may actually be setting the stage" for dementia, says Jeffrey Iliff, a brain scientist at Oregon Health & Science University in Portland.

The brain appears to clear out toxins linked to Alzheimer's during sleep, Iliff explains. And, at least among research animals that don't get enough solid shut-eye, those toxins can build up and damage the brain.

Iliff and other scientists at OHSU are about to launch a study of people that should clarify the link between sleep problems and Alzheimer's disease in humans.

It has been clear for decades that there is some sort of link. Sleep disorders are very common among people with Alzheimer's disease.

For a long time, researchers thought this was simply because the disease was "taking out the centers of the brain that are responsible for regulating sleep," Iliff says. But two recent discoveries have suggested the relationship may be more complicated.

The first finding emerged in 2009, when researchers at Washington University in St. Louis showed that the sticky amyloid plaques associated with Alzheimer's develop more quickly in the brains of sleep-deprived mice.

Then, in 2013, Iliff was a member of a team that discovered how a lack of sleep could be speeding the development of those Alzheimer's plaques: A remarkable cleansing process takes place in the brain during deep sleep, at least in animals.

What happens, Iliff says, is "the fluid that's normally on the outside of the brain, cerebrospinal fluid — it's a clean, clear fluid — it actually begins to recirculate back into and through the brain along the outsides of blood vessels."

This process, via what's known as the glymphatic system, allows the brain to clear out toxins, including the toxins that form Alzheimer's plaques, Iliff says.

Scientists watch dye flow through the brain of a sleeping mouse.Nedergaard Lab, University of Rochester Medical Center.

"That suggests at least one possible way that disruption in sleep may predispose toward Alzheimer's disease," he says.

To know for sure, though, researchers will have to study this cleansing process in people, which won't be easy.

Iliff studied the glymphatic system in living mice by looking through a window created in the skull. The system also involved a powerful laser and state-of-the-art microscope.

With people, "we have to find a way to see the same sort of function, but in a way that is going to be reasonably noninvasive and safe," he says.

The solution may involve one of the world's most powerful magnetic resonance imaging machines, which sits in a basement at OHSU. The MRI unit is so sensitive, it should be able to detect changes that indicate precisely when the glymphatic system gets switched on in a person's brain, says Bill Rooney, who directs the university's Advanced Imaging Research Center.

When humans enter deep sleep, and toxin removal begins, there should be a particular change in the signal coming from certain salt molecules. That would indicate that fluid has begun moving freely through the brain.

In young, healthy brains, the signal should be "robust," Rooney says, indicating that the toxin removal system is working well. In the brains of older people, and those who are likely to develop Alzheimer's, the signal should be weaker.

Rooney and Iliff have received funding from the Paul G. Allen Foundation to test their approach. They hope to begin scanning the brains of participants within a year.

One challenge, though, will be finding people able to fall asleep in the cramped and noisy tunnel of the magnetic resonance machine.

"It's a tricky thing because it's a small space," Rooney says. "But we'll make people as comfortable as possible, and we'll just follow them as they go through these natural stages of sleep."

If Rooney and Iliff are right, the experiment will greatly strengthen the argument that a lack of sleep can lead to Alzheimer's disease. It might also provide a way to identify people whose health is at risk because they aren't getting enough deep sleep, and it could pave the way to new treatments.

"It could be anything from having people exercise more regularly, or new drugs," Rooney says. "A lot of the sleep aids don't particularly focus on driving people to deep sleep stages."