Not All Sleep is Equal When It
Comes to Cleaning the Brain
University of Rochester – February 27, 2019 -- New
research shows how the depth of sleep can impact our brain’s ability to
efficiently wash away waste and toxic proteins. Because sleep often becomes
increasingly lighter and more disrupted as we become older, the study
reinforces and potentially explains the links between aging, sleep deprivation,
and heightened risk for Alzheimer’s disease.
“Sleep is critical to the function of the brain’s waste removal system and
this study shows that the deeper the sleep the better,” said Maiken Nedergaard,
M.D., D.M.Sc., co-director of the Center for Translational
Neuromedicine at the University of Rochester Medical Center (URMC) and lead
author of the study. “These findings also add to the increasingly clear
evidence that quality of sleep or sleep deprivation can predict the onset of
Alzheimer’s and dementia.”
The study, which appears in the journal Science Advances, indicates
that the slow and steady brain and cardiopulmonary activity associated with
deep non-REM sleep are optimal for the function of the glymphatic system, the
brain’s unique process of removing waste. The findings may also explain why
some forms of anesthesia can lead to cognitive impairment in older
adults.
The previously unknown glymphatic system was first
described by Nedergaard and her colleagues in 2012. Prior to that
point, scientists did not fully understand how the brain, which maintains its
own closed ecosystem, removed waste. The study revealed a system of
plumbing which piggybacks on blood vessels and pumps cerebral spinal fluid
(CSF) through brain tissue to wash away waste. A subsequent study showed
that this system primarily
works while we sleep.
Because the accumulation of toxic proteins such as beta amyloid and tau in
the brain are associated with Alzheimer’s disease, researchers have speculated
that impairment of the glymphatic system due to disrupted sleep could be a
driver of the disease. This squares with clinical observations which show
an association between sleep deprivation and heightened risk for
Alzheimer’s.
In the current study, researchers conducted experiments with mice that were
anesthetized with six different anesthetic regimens. While the animals
were under anesthesia, the researchers tracked brain electrical activity,
cardiovascular activity, and the cleansing flow of CSF through the
brain. The team observed that a combination of the drugs ketamine and
xylazine (K/X) most closely replicated the slow and steady electrical activity
in the brain and slow heart rate associated with deep non-REM sleep.
Furthermore, the electrical activity in the brains of mice administered K/X
appeared to be optimal for function of the glymphatic system.
“The synchronized waves of neural activity during deep slow-wave sleep,
specifically firing patterns that move from front of the brain to the back,
coincide with what we know about the flow of CSF in the glymphatic system,”
said Lauren Hablitz, Ph.D., a postdoctoral associate in Nedergaard’s lab and
first author of the study. “It appears that the chemicals involved in the
firing of neurons, namely ions, drive a process of osmosis which helps pull the
fluid through brain tissue.”
The study raises several important clinical questions. It further
bolsters the link between sleep, aging, and Alzheimer’s disease. It is
known that as we age it becomes more difficult to consistently achieve deep
non-REM sleep, and the study reinforces the importance of deep sleep to the proper
function of the glymphatic system. The study also demonstrates that the
glymphatic system can be manipulated by enhancing sleep, a finding that may
point to potential clinical approaches, such as sleep therapy or other methods
to boost the quality of sleep, for at-risk populations.
Furthermore, because several of the compounds used in the study were
analogous to anesthetics used in clinical settings, the study also sheds light
on the cognitive difficulties that older patients often experience after surgery
and suggests classes of drugs that could be used to avoid this phenomenon.
Mice in the study that were exposed to anesthetics that did not induce
slow brain activity saw diminished glymphatic activity.
“Cognitive impairment after anesthesia and surgery is a major problem,”
said Tuomas Lilius, M.D., Ph.D., with the Center for Translational
Neuromedicine at the University of Copenhagen in Denmark and co-author of the
study. “A significant percentage of elderly patients that undergo
surgery experience a postoperative period of delirium or have a new or worsened
cognitive impairment at discharge.”
Additional co-authors of the study include Hanna Vinitsky and Qian Sun with
URMC, and Frederik Filip Staeger, Bjorn Sigurdsson, and Kristian Mortensen with
the University of
Copenhagen .