Without sufficient sleep, mood and cognition are impaired. Various 
central nervous system conditions, including migraines and seizures, 
become more frequent and severe. When animals are kept from sleeping, 
they ultimately die.

We need to sleep. But why? Investigators from New York developed a 
technique for measuring the interstitial space in the brains of living 
mice. That space is bathed by cerebrospinal fluid that is produced by 
the choroid plexus and pumped back into the blood in the meninges. The 
investigators found that, during sleep and anesthesia, the 
interstitial space increased by 60%. The functional result of this 
expansion is that many metabolites of neurons and glial cells that 
spill into the interstitial space are cleared from the space much more 
rapidly, enter the blood, and are detoxified by the liver. These 
molecules include β-amyloid and tau, which build up in the brains of 
patients with Alzheimer disease. When sleeping animals are aroused, 
clearance of toxic metabolites slows markedly.

COMMENT

The investigators speculate that, at least in mice, buildup of toxic 
metabolites in the brain’s interstitial space is a trigger for sleep 
and that a key purpose of sleep is to clear such metabolites. Perhaps 
we feel restored in the morning because the brain has freed itself of 
toxins. This hypothesis is arresting in its simplicity and could prove 
to be profoundly important in human biology.

Xie L et al. Science 2013 Oct 18. 
Herculano-Houzel S. Science 2013 Oct 18.