Both were done in mice, so it's too soon to know if humans respond similarly. But they raise disturbing questions about the toll our 24-hour society may be taking on our brains.
"Until we know more, maybe we better think a little bit more about our sleep," said Sigrid Veasey, an associate professor in Penn's Center for Sleep and Circadian Neurobiology. Her study found that sleep-deprived mice had problems even when they had a chance to make up some of the sleep they'd lost.
Domenico Pratico, the Temple Alzheimer's researcher who studied mice modified to develop the memory-robbing disease, agreed that people would be wise to think of getting six to eight hours of sleep a night as being as important to health as a good diet and vigorous exercise.
Sleep problems have long been linked to Alzheimer's, but doctors don't know whether they are a cause or symptom of the disease.
Pratico's eight-week study used mice that develop Alzheimer's at 14 to 15 months old. When they were 6 months old, he exposed some of them to a normal schedule of 12 hours of light and 12 hours of darkness. Others got 20 hours of light and four hours of darkness. It's hard to tell when mice are sleeping, but Pratico said they normally are quiet about half the day. The mice exposed to more light were active about 75 percent of the day.
After the trial, the sleep-deprived mice did 40 to 50 percent worse on tests of learning and memory than the mice that had been on a normal schedule. Also, the Temple team found significant changes in tau protein in their brains. We all have tau in its normal form, but a tangled, misshapen variant is a hallmark of Alzheimer's. Pratico's group found an insoluble form that is a precursor to tangles. They also found that brain cells were not communicating with each other normally.
Pratico believes the changes are irreversible.
Veasey was interested in why people seem to take so long to recover from lost sleep, even when they get a chance to catch up.
Her Penn group studied locus coeruleus neurons, a small group of neurons - mice have about 3,000 of them and humans more like 200,000 - in the brain stem. Some have thousands of axons - fibers that transmit messages - that fan out to every part of the cortex.
Veasey's mice lost about four hours of sleep a day over just three days. Her team kept them awake during eight hours of their usual sleep time by stroking them gently and adding interesting toys to their cages. The mice were then allowed to sleep, but they only made up about four of the hours they lost. Veasey said this is typical of human shift workers' experience.
Her group found that, in the short term, the locus coeruleus neurons used more of a protein called SirT3 that helps increase cellular energy and protect cells against damage. That didn't happen with extended wakefulness. After the test, the mice had lost 25 percent of these neurons.
Veasey said she is concerned about young adults, who often pull all-nighters and think they can recover by sleeping late on weekends.
On the plus side, she said SirT3 has potential as a treatment for preventing damage from sleep loss.