The study shows disturbing evidence that chronic sleep loss may lead to irreversible physical damage to and loss of brain cells.
Using a mouse model of chronic sleep loss, Sigrid Veasey, from University of Pennsylvania School of Medicine and collaborators from Peking University, have determined that extended wakefulness is linked to injury to, and loss of, neurons that are essential for alertness and optimal cognition, the locus coeruleus (LC) neurons.
"In general, we've always assumed full recovery of cognition following short- and long-term sleep loss," Veasey said.
"But some of the research in humans has shown that attention span and several other aspects of cognition may not normalise even with three days of recovery sleep, raising the question of lasting injury in the brain," Veasey said.
Mice were examined following periods of normal rest, short wakefulness, or extended wakefulness, modeling a shift worker's typical sleep pattern.
Researchers found that in response to short-term sleep loss, LC neurons up-regulate the sirtuin type 3 (SirT3) protein, which is important for mitochondrial energy production and redox responses, and protect the neurons from metabolic injury.
SirT3 is essential across short-term sleep loss to maintain metabolic homoeostasis, but in extended wakefulness, the SirT3 response is missing, researchers said.
After several days of shift worker sleep patterns, LC neurons in the mice began to display reduced SirT3, increased cell death, and the mice lost 25 per cent of these neurons.
"This is the first report that sleep loss can actually result in a loss of neurons," Veasey said.
The findings suggest that mitochondria in LC neurons respond to sleep loss and can adapt to short-term sleep loss but not to extended wake.
This raises the possibility that somehow increasing SirT3 levels in the mitochondria may help rescue neurons or protect them across chronic or extended sleep loss.
The study also demonstrates the importance of sleep for restoring metabolic homoeostasis in mitochondria in the LC neurons and possibly other important brain areas, to ensure their optimal functioning during waking hours.
Veasey stresses that more work needs to be done to establish whether a similar phenomenon occurs in humans and to determine what durations of wakefulness place individuals at risk of neural injury.
The research is published in The Journal of Neuroscience.