New research suggests chronic sleep deprivation could cause irreversible damage or loss of brain cells.

The team used a mouse model of sleep deprivation and found extended wakefulness was linked to a reduction in the neurons responsible for "alertness and optimal cognition," a University of Pennsylvania School of Medicine news release reported.

"In general, we've always assumed full recovery of cognition following short- and long-term sleep loss," Sigrid Veasey, MD, associate professor of Medicine and a member of the Center for Sleep and Circadian Neurobiology at the Perelman School of Medicine and collaborators from Peking University, said in the news release. "But some of the research in humans has shown that attention span and several other aspects of cognition may not normalize even with three days of recovery sleep, raising the question of lasting injury in the brain. We wanted to figure out exactly whether chronic sleep loss injures neurons, whether the injury is reversible, and which neurons are involved."

Researchers observed the mice after periods of "normal rest, short wakefulness, or extended wakefulness," the news release reported. The period of extended wakefulness mimicked the life lived by the average shift worker.  

The team found in cases of sleep loss locus coeruleus (LC) neurons "upregulated" the sirtuin type 3 (SirT3) proteins, which protect the neurons from injury. In periods of extended wakefulness the SirT3 response was reduced.  Extended periods of wakefulness led to a loss of about 25 percent of neurons.

"This is the first report that sleep loss can actually result in a loss of neurons," Veasey said.

 Mitochondria in LC neurons were found to be resilient to short term sleep loss, but not extended wakefulness. The finding suggests increasing SirT3 levels could help protect neurons from damage caused by extended wakefulness.

 "In light of the role for SirT3 in the adaptive response to sleep loss, the extent of neuronal injury may vary across individuals. Specifically, aging, diabetes, high-fat diet and sedentary lifestyle may all reduce SirT3. If cells in individuals, including neurons, have reduced SirT3 prior to sleep loss, these individuals may be set up for greater risk of injury to their nerve cells," Veasey said.

In the future the team hopes to test out the new SirT3 model.

"We can now overexpress SirT3 in LC neurons," Veasey said. "If we can show that we can protect the cells and wakefulness, then we're launched in the direction of a promising therapeutic target for millions of shift workers."