Goodnight. Sleep Clean.
SLEEP
seems like a perfectly fine waste of time. Why would our bodies evolve
to spend close to one-third of our lives completely out of it, when we
could instead be doing something useful or exciting? Something that
would, as an added bonus, be less likely to get us killed back when we
were sleeping on the savanna?
“Sleep
is such a dangerous thing to do, when you’re out in the wild,” Maiken
Nedergaard, a Danish biologist who has been leading research into sleep
function at the University of Rochester’s medical school, told me. “It
has to have a basic evolutional function. Otherwise it would have been
eliminated.”
We’ve known for some time that sleep is essential for forming and consolidating memories and that it plays a central role
in the formation of new neuronal connections and the pruning of old
ones. But that hardly seems enough to risk
death-by-leopard-in-the-night. “If sleep was just to remember what you
did yesterday, that wouldn’t be important enough,” Dr. Nedergaard
explains.
In a series of new studies, published
this fall in the journal Science, the Nedergaard lab may at last be
shedding light on just what it is that would be important enough. Sleep,
it turns out, may play a crucial role in our brain’s physiological
maintenance. As your body sleeps, your brain is quite actively playing
the part of mental janitor: It’s clearing out all of the junk that has
accumulated as a result of your daily thinking.
Recall
what happens to your body during exercise. You start off full of
energy, but soon enough your breathing turns uneven, your muscles tire,
and your stamina runs its course. What’s happening internally is that
your body isn’t able to deliver oxygen quickly enough to each muscle
that needs it and instead creates needed energy anaerobically. And while
that process allows you to keep on going, a side effect
is the accumulation of toxic byproducts in your muscle cells. Those
byproducts are cleared out by the body’s lymphatic system, allowing you
to resume normal function without any permanent damage.
The
lymphatic system serves as the body’s custodian: Whenever waste is
formed, it sweeps it clean. The brain, however, is outside its reach —
despite the fact that your brain uses up about 20 percent of your body’s
energy. How, then, does its waste — like beta-amyloid, a protein
associated with Alzheimer’s disease — get cleared? What happens to all
the wrappers and leftovers that litter the room after any mental
workout?
“Think
about a fish tank,” says Dr. Nedergaard. “If you have a tank and no
filter, the fish will eventually die. So, how do the brain cells get rid
of their waste? Where is their filter?”
UNTIL
a few years ago, the prevailing model was based on recycling: The brain
got rid of its own waste, not only beta-amyloid but other metabolites,
by breaking it down and recycling it at an individual cell level. When
that process eventually failed, the buildup would result in age-related
cognitive decline and diseases like Alzheimer’s. That “didn’t make
sense” to Dr. Nedergaard, who says that “the brain is too busy to
recycle” all of its energy. Instead, she proposed
a brain equivalent of the lymphatic system, a network of channels that
cleared out toxins with watery cerebrospinal fluid. She called it the
glymphatic system, a nod to its dependence on glial cells (the
supportive cells in the brain that work largely to maintain homeostasis
and protect neurons) and its function as a sort of parallel lymphatic
system.
She
was hardly the first to think in those terms. “It had been proposed
about one hundred years ago, but they didn’t have the tools to study it
properly,” she says. Now, however, with advanced microscopes and dyeing
techniques, her team discovered that the brain’s interstitial space —
the fluid-filled area between tissue cells that takes up about 20
percent of the brain’s total volume — was mainly dedicated to physically
removing the cells’ daily waste.
When
members of Dr. Nedergaard’s team injected small fluorescent tracers
into the cerebrospinal fluid of anesthetized mice, they found that the
tracers quickly entered the brain — and, eventually, exited it — via
specific, predictable routes.
The
next step was to see how and when, exactly, the glymphatic system did
its work. “We thought this cleaning process would require tremendous
energy,” Dr. Nedergaard says. “And so we asked, maybe this is something
we do when we’re sleeping, when the brain is really not processing
information.”
In
a series of new studies on mice, her team discovered exactly that: When
the mouse brain is sleeping or under anesthesia, it’s busy cleaning out
the waste that accumulated while it was awake.
In
a mouse brain, the interstitial space takes up less room than it does
in ours, approximately 14 percent of the total volume. Dr. Nedergaard
found that when the mice slept, it swelled to over 20 percent. As a
result, the cerebrospinal fluid could not only flow more freely but it
could also reach further into the brain. In an awake brain, it would
flow only along the brain’s surface. Indeed, the awake flow was a mere 5
percent of the sleep flow. In a sleeping brain, waste was being cleared
two times faster. “We saw almost no inflow of cerebrospinal fluid into
the brain when the mice were awake, but then when we anesthetized them,
it started flowing. It’s such a big difference I kept being afraid
something was wrong,” says Dr. Nedergaard.
Similar
work in humans is still in the future. Dr. Nedergaard is currently
awaiting board approval to begin the equivalent study in adult brains in
collaboration with the anesthesiologist Helene Benveniste at Stony
Brook University.
So
far the glymphatic system has been identified as the neural housekeeper
in baboons, dogs and goats. “If anything,” Dr. Nedergaard says, “it’s
more needed in a bigger brain.”
MODERN
society is increasingly ill equipped to provide our brains with the
requisite cleaning time. The figures are stark. Some 80 percent of
working adults suffer to some extent from sleep deprivation. According to the National Sleep Foundation, adults should sleep seven to nine hours. On average,
we’re getting one to two hours less sleep a night than we did 50 to 100
years ago and 38 minutes less on weeknights than we did as little as 10
years ago. Between 50 and 70 million people in the United States suffer
from some form of chronic sleep disorder. When our sleep is disturbed,
whatever the cause, our cleaning system breaks down. At the University
of Pennsylvania’s Center for Sleep and Circadian Neurobiology, Sigrid
Veasey has been focusing
on precisely how restless nights disturb the brain’s normal metabolism.
What happens to our cognitive function when the trash piles up?
At
the extreme end, the result could be the acceleration of
neurodegenerative diseases like Alzheimer’s and Parkinson’s. While we
don’t know whether sleep loss causes the disease, or the disease itself
leads to sleep loss — what Dr. Veasey calls a “classic chicken-and-egg”
problem — we do know that the two are closely connected. Along with the
sleep disturbances that characterize neurodegenerative diseases, there
is a buildup of the types of proteins that the glymphatic system
normally clears out during regular sleep, like beta-amyloids and tau,
both associated with Alzheimer’s and other types of dementia.
“To
me,” says Dr. Veasey, “that’s the most compelling part of the
Nedergaard research. That the clearance for these is dramatically
reduced from prolonged wakefulness.” If we don’t sleep well, we may be
allowing the very things that cause neural degeneration to pile up
unchecked.
Even
at the relatively more benign end — the all-nighter or the
extra-stressful week when you caught only a few hours a night — sleep
deprivation, as everyone who has experienced it knows, impedes our
ability to concentrate, to pay attention to our environment and to
analyze information creatively. “When we’re sleep-deprived, we can’t
integrate or put together facts,” as Dr. Veasey puts it.
But
there is a difference between the kind of fleeting sleep loss we
sometimes experience and the chronic deprivation that comes from shift
work, insomnia and the like. In one set of studies, soon to be published
in The Journal of Neuroscience, the Veasey lab found that while our
brains can recover quite readily from short-term sleep loss, chronic
prolonged wakefulness and sleep disruption stresses the brain’s
metabolism. The result is the degeneration of key neurons involved in
alertness and proper cortical function and a buildup of proteins
associated with aging and neural degeneration.
It’s
like the difference between a snowstorm’s disrupting a single day of
trash pickup and a prolonged strike. No longer quite as easy to fix, and
even when the strike is over, there’s likely to be some stray debris
floating around for quite some time yet. “Recovery from sleep loss is
slower than we’d thought,” Dr. Veasey notes. “We used to think that
after a bit of recovery sleep, you should be fine. But this work shows
you’re not.”
If
you put her own research together with the findings from the Nedergaard
lab, Dr. Veasey says, it “very clearly shows that there’s impaired
clearance in the awake brain. We’re really starting to realize that when
we skip sleep, we may be doing irreparable damage to the brain,
prematurely aging it or setting it up for heightened vulnerability to
other insults.”
In
a society that is not only chronically sleep-deprived but also rapidly
aging, that’s bad news. “It’s unlikely that poor sleep as a child would
actually cause Alzheimer’s or Parkinson’s,” says Dr. Veasey, “but it’s
more likely that you may shift one of those diseases by a decade or so.
That has profound health and economic implications.”
It’s
a pernicious cycle. We work longer hours, become more stressed, sleep
less, impair our brain’s ability to clean up after all that hard work,
and become even less able to sleep soundly. And if we reach for a
sleeping pill to help us along? While work on the effects of sleeping
aids on the glymphatic system remains to be done, the sleep researchers I
spoke with agree that there’s no evidence that aided sleep is as
effective as natural sleep.
There
is, however, reason to hope. If the main function of sleep is to take
out our neural trash, that insight could eventually enable a new
understanding of both neurodegenerative diseases and regular,
age-related cognitive decline. By developing a diagnostic test to
measure how well the glymphatic system functions, we could move one step
closer to predicting someone’s risk of developing conditions like
Alzheimer’s or other forms of dementia: The faster the fluids clear the
decks, the more effectively the brain’s metabolism is functioning.
“Such
a test could also be used in the emergency room after traumatic brain
injury,” Dr. Nedergaard says, “to see who is at risk of developing
decline in cognitive function.”
We
can also focus on developing earlier, more effective interventions to
prevent cognitive decline. One approach would be to enable individuals
who suffer from sleep loss to sleep more soundly — but how? Dr.
Nedergaard’s mice were able to clear their brain’s waste almost as
effectively under anesthesia as under normal sleeping conditions.
“That’s really fascinating,” says Dr. Veasey. Though current sleeping
aids may not quite do the trick, and anesthetics are too dangerous for
daily use, the results suggest that there may be better ways of
improving sleep pharmacologically.
Now
that we have a better understanding of why sleep is so important, a new
generation of drug makers can work to create the best possible
environment for the trash pickup to occur in the first place — to make
certain that our brain’s sleeping metabolism is as efficient as it can
possibly be.
A
second approach would take the opposite tack, by seeking to mimic the
cleanup-promoting actions of sleep in the awake brain, which could make a
full night of sound sleep less necessary. To date, the brain’s
metabolic process hasn’t been targeted as such by the pharmaceutical
industry. There simply wasn’t enough evidence of its importance. In
response to the evolving data, however, future drug interventions could
focus directly on the glymphatic system, to promote the enhanced
cleaning power of the sleeping brain in a brain that is fully awake. One
day, scientists might be able to successfully mimic the expansion of
the interstitial space that does the mental janitorial work so that we
can achieve maximally efficient round-the-clock brain trash pickup.
If
that day comes, they would be on their way to discovering that all-time
miracle drug: one that, in Dr. Veasey’s joking words, “could mean we
never have to sleep at all.”
Maria Konnikova is the author of “Mastermind: How to Think Like Sherlock Holmes.”
A version of this op-ed appears in print on January 12, 2014, on page SR1 of the New York edition with the headline: Goodnight. Sleep Clean.
http://www.nytimes.com/2014/01/12/opinion/sunday/goodnight-sleep-clean.html
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