Australasian Science: Australia's authority on science since 1938

To Sleep, Perchance to Clean the Brain

By Tim Hannan

The restorative function of a night’s sleep may result from elimination of the day’s neurotoxins.

While those who mark World Sleep Day are probably disinclined to do so with all-night parties, neuroscientists may have celebrated it this year more enthusiastically with the news that one of biology’s great mysteries may have been solved.

Despite advances in understanding the architecture and neurobiology of sleep, a satisfactory answer to the question of why humans and other animals sleep had long proven elusive. Now, a new study has found evidence for the proposition that sleep facilitates the removal of potentially toxic products in the brain – that is, that the brain cleans itself while we sleep.

Like most animals, humans operate on a daily cycle of alternating activity and sleep, and it is evident that sleep serves a restorative function of some kind: the need to sleep increases with time since its last occurrence, and generally people do not function well without sleep.

It is well-established that sleep deprivation is associated with impaired performance on cognitive tests, including a longer reaction time to stimuli, and that prolonged deprivation may result in progressively worsening cognition and even death. Yet precisely how sleep is restorative, and why the lack of sleep impairs brain function, has remained unknown.

In the study published in Science, a team of American researchers investigated the hypothesis that sleep enhances the removal of potentially toxic molecules that accumulate in the space between brain cells.

The researchers’ previous studies with rodents had established that the brain has a unique waste removal system in which cerebrospinal fluid is pumped through the space between cells, flushing waste products into the circulatory system and via the bloodstream to the liver. This glymphatic system presumably requires considerable expenditure of energy, and the researchers speculated that its operation may not be compatible with the demands of the cognitive information-processing system of the awake brain. As one of the research team remarked in an interview, when throwing a party you can either entertain guests or clean up after them, but you can’t do both at the same time.

The researchers tested this by injecting a protein labelled with a radioactive dye into the brains of mice, and observed its rate of removal while the animals were either awake or asleep. The protein employed was beta-amyloid, which has been linked to degenerative diseases, including Alzheimer’s disease.

They found that beta-amyloid disappeared much faster when the mice were asleep or anaesthetised, with the glymphatic system up to 10 times more active when asleep than awake. That the effect was observed during anaesthesia suggests that it is not the diurnal sleep–wake cycle per se that is associated with the removal of waste products, but the sleep state itself.

Another important finding was the observation of a dramatic increase in the space surrounding brain cells during sleep or anaesthesia. This interstitial space expanded by up to 60%, reflecting a contraction of brain cells that enables the glymphatic system to pump cerebrospinal fluid more freely through the brain.

The researchers also noted that when a noradrenaline inhibitor was administered, interstitial space increased in awake mice. This prompted the hypothesis that noradrenaline, which is associated with alertness, plays a major role in regulating the contraction of brain cells during sleep.

This association between the sleep state and the removal of accumulated waste products offers the hope of advances in the understanding and treatment of neurodegenerative disorders linked to beta-amyloid and other toxic molecules.

On average we spend about 27 years of our lives asleep, and its demonstrated associations with physical and mental well-being have motivated sleep psychologists and physicians to promote good sleep as one of the three pillars of a healthy life, along with regular exercise and a balanced diet.

This new finding that the brain enters a “washing cycle” during sleep sheds light on the mystery of its evolution and function, opens new lines of enquiry into degenerative disorders, and adds a new meaning to the adage that sleep is a great way to clear the mind.

Tim Hannan is an Associate Professor of Clinical Psychology at Charles Sturt University, and the President of the Australian Psychological Society.