For centuries biologists have speculated about why we sleep. It has been a pressing question in part because sleep seems so maladaptive. As an evolving species that was more prey than predator, passing the night in an unconscious state sounds like a very bad idea. Sleep provides no food or shelter and consumes one-third of our lives. And yet, we have no choice. Every animal must sleep. Deprived of this mysterious state, we perish.
Our appreciation of the consequences of sleep loss has grown over the last 50 years and now includes impaired learning, memory, decision making, and reaction time, increased risk of hypertension, seizure and migraine and many more. This sprawling list clearly demonstrates that sleep deprivation impairs brain function.
So we understand that sleep is essential. But the question remains, what happens in sleep that allows for the maintenance of normal function?
Lulu Xie's research group at the University of Rochester Medical Center in New York may have found the answer. In a remarkable series of experiments they observed a dramatic increase in the removal of toxic waste products in the sleeping state that had accumulated in the waking brain. All neurodegenerative diseases are associated with the accumulation of these waste products. Sleep appears to allow a cleansing of the brain.
The clearing of byproducts of cellular metabolism is an important function throughout the body in order to prevent injury. The lymphatic system, which runs parallel to blood vessels, provides the cleansing stream that flushes this debris from the body. Generally, the more active (higher metabolic rate and therefore more byproduct created) a tissue, the denser the lymphatic coverage.
The brain is a curious exception to this rule. Despite a very high metabolic rate, it has no lymph vessels. Because nerve cells are particularly sensitive to toxic waste products, the removal of this cellular garbage is critical. Until recently, there was no good explanation of how this is accomplished.
In 2012, Iliff et al. discovered a lymph-like system that bathes the brain. This network was named the glymphatic system, a complex system of passages that allows cerebrospinal fluid to access intercellular spaces and remove waste material.
Building on Iliff's findings, Xie's group demonstrated a dramatic increase in glymphatic flow during sleep. They hypothesize that adrenalin plays a central role. Arousal is driven to a large extent by the adrenergic signaling system, which shifts the brain into a waking state. Xie suggests that adrenalin triggers an increase in brain cell size thereby shrinking the space between cells. This closes glymphatic passages during the waking state. With the withdrawal of adrenergic signaling during sleep, these passages open and allow a cleansing sweep of the debris that built up during the day.
These findings have enormous implications. It opens new possibilities for the treatment of all neurodegenerative diseases. This includes Alzheimer's disease, a condition caused by a failure to clear soluble proteins from the brain.
This work also sheds light on the pathological consequences of sleep deprivation.
Sleep it out is the new sleep it off.