Late-shift workers, students and other night owls take note – a new sleep study from researchers at the University of Pennsylvania has shown for the first time that extended periods of sleeplessness can lead to irreversible brain damage.
While previous studies have shown cognitive performance
declines after sleep loss, the latest research challenges the long-held notion that a "sleep debt" could be recovered by makeup rest. Researchers
at UPenn and collaborators at Peking University have found extended periods of wakefulness
actually kill some neurons and cause damage to others.
Scientists knew there were certain neurons in the brain stem that are awake when we are awake and "sleep when we sleep," says Dr. Sigrid Veasey, a study author and professor at UPenn's Perelman School of Medicine.
“This gave us an indication that maybe [the cells] needed their rest,” she says. “We hypothesized that the cells that were going to be the most likely to get injured would be some of the cells that are active during wakefulness.”
These particular neurons located in the brain stem are critical to attention, cognitive performance and also play a role in determining one’s mood.
“So if there’s an injury to these neurons, then you may have poor ability to pay attention and you might also have depression,” Veasey says.
Veasey and her colleagues used a mouse model to explore the impact of imposed wakefulness on mice’s brains. They separated mice into three groups. One group was allowed sleep as usual, another group was kept awake for three additional hours during their normal sleep period in a space outfitted with "play" items – wheels, toys and other mice. A third group of mice was kept awake in a similar environment during their normal sleep period for an additional eight hours, for three days.
Humans and other mammals share these same neural networks, so looking at wakefulness in mice is a good proxy for understanding the sleep habits of humans.
“There’s every indication that they function the same way,” says Veasey.
After procuring brain tissue from the mice, researchers found an increase in the amount of a protein known as SirT3, that protects these "wake-active neurons" from damage among the mice who were kept from sleeping for shortened periods, but the mice who were kept awake for extended periods did not show any increase in this protective protein. Researchers also found a 25 to 30 percent loss of neurons and an increase in what’s known as oxidative stress in the extended wakefulness group of mice. This stress causes the proteins inside these neurons to fold on top of each other and can prevent them from communicating with other neurons. Some of the mice had a genetic deletion which stopped them from producing this key protein. Those mice also incurred damage to these sleep-sensitive neurons, even with only short-term sleep loss.
“So really the cells that are remaining just don’t function well,” says Veasey.
The results of the study emphasize the critical importance of sleep, says Veasey.
“You can push the system a little bit, but you can’t push it too hard and for too long or you’ll have irreversible consequences,” she says.
For students, academics and other professionals looking to gain an edge, Veasey says, “You’re at a time in your life when you really have to pull a couple of all-nighters to sustain that edge academically or professionally, but by cutting our sleep times short then do we end up losing that edge in the long term because we lose those neurons that are so critical for attention?”
Veasey says while she can't repeat this study in humans, there is certainly room for more research.
In addition, having learned the critical importance of this protective protein SirT3, researchers believe that it could provide avenues for new treatment.
"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," said Veasey in a press release.
Future studies could use brain imaging techniques to look at people with sleeping disorders to help researchers better understand the damage that's incurred through sleep loss.
The study was first published Tuesday in the Journal of Neuroscience.