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Sure You're Awake? Spit into this Cup

For release: Friday, March 9, 2007

If a jolty ride on public transportation has ever left you wondering whether the driver was dozing off at the wheel, consider the results of a new study that suggests sleepiness might one day be measured by taking a saliva sample.

The study, published in the Proceedings of the National Academy of Sciences,* identifies a chemical in saliva whose levels go up when people are sleep-deprived and down when they are rested. The chemical could be used as a "biomarker" to gauge sleepiness in a variety of occupational settings where tired workers are likely to put themselves and others at risk, said the study's senior author, Paul J. Shaw, Ph.D., a professor of anatomy and neurobiology at Washington University School of Medicine in St. Louis.

Dr. Shaw's work and other studies on the basic mechanisms of sleep fill an important public health need, said Merrill Mitler, Ph.D., a program director in the Division of Extramural Research at the National Institute of Neurological Disorders and Stroke (NINDS).

"Excessive sleepiness troubles millions of Americans. It can be the result of sleep apnea or another disorder, a side effect of medication, or simply the product of a demanding work schedule," Dr. Mitler said. "Whatever the cause, insufficient sleep can create significant health risks, both for the affected person and others."

Among the many situations where a lack of sleep could be dangerous, driving stands out as the most statistically relevant. The National Highway Traffic Safety Administration estimates that sleepiness may be a factor in 20 percent of motor vehicle crashes, some of which probably can be traced to the long hours that truckers are expected to spend behind the wheel. Sleep deprivation among medical personnel, especially young residents, has become a major concern at hospitals. Indeed, sleep-related accidents have generated a spate of malpractice lawsuits, leading some hospitals to impose tighter limits over the hours their residents work.

An obvious way to find out if people are sleep-deprived is to ask them, or to look for visible signs of sleepiness (bloodshot eyes, slurred speech, poor attention). But these approaches often miss the truth, said Dr. Shaw.

"People tend not to admit they're tired," he said. "And the overt signs that someone is sleepy tend to happen long after he's already in trouble. We want to identify people who are tired before something bad happens."

Dr. Shaw, who is supported by NINDS, began his search for a biomarker of sleepiness in fruit flies. Although they can do it clinging to a wall, flies sleep in a manner reminiscent of other animals, he said. They become quiet and still for about 90 minutes at a time, sleeping about 12 hours total each day. Their well-characterized genetics, and the ability to study mutant flies with altered sleep behavior, facilitated Dr. Shaw's search.

Dr. Shaw first used a DNA microarray - a chip coated with thousands of genetic probes - to scan for genes whose activity was altered in sleep-deprived flies. Activity of the gene encoding amylase - a protein in animal saliva that helps digest starch - consistently spiked in flies that were kept awake.

In another set of experiments, Dr. Shaw measured the activity of the amylase gene relative to the flies' sleep patterns by probing for amylase RNA - the chemical intermediate necessary to convert the amylase gene into protein. He showed that amylase RNA levels increase specifically prior to a condition known as "sleep rebound" - a period of deep slumbering that satisfies the need for sleep. The experiments were important for establishing amylase as a biomarker for sleepiness, he said, because many genes might be expected to turn on in an awake fly (or person), even one that isn't feeling sleepy.

Dr. Shaw collaborated with Stephen Duntley, M.D., a professor of neurology at Washington University's Sleep Medicine Center, to determine if amylase levels are a surrogate for sleepiness in people. Nine volunteers were monitored at the sleep center during a weekend of normal sleep, and during a weekend when they went without sleep for 28 hours. Amylase RNA was probed in the participants' saliva. Drs. Shaw and Duntley found that in people, as in flies, the RNA levels climbed during sleep deprivation.

In addition to identifying people who are at risk for sleep-related accidents, Dr. Shaw speculated that amylase levels in saliva could be used to measure sleepiness in research on the mechanisms of sleep. The need for sleep varies widely among people and among animal species, he said, and a biomarker for sleepiness could help researchers sort out the genetic basis for those differences. Electroencephalography (EEG) can be used to record brain waves that herald the onset of sleep, but the technique is time-consuming and not always practical.

"It's hard to put electrodes on a killer whale," Dr. Shaw said, noting that whales can go for extended periods without sleeping.

"Our immediate goal is to shift the focus away from amylase toward identifying other biomarkers," he said. A panel of biomarkers could be cross-checked against each other, he explained, giving researchers the most accurate assessments of when people, flies, and other creatures are in need of a good night's sleep.

*Seugnet L, Boero J, Gottschalk L, Duntley SP, and Shaw PJ. "Identification of a Biomarker for Sleep Drive in Flies and Humans." Proceedings of the National Academy of Sciences. December 26, 2006, Vol. 103(52), pp. 19913-19918.

-By Daniel Stimson, Ph.D.

Last Modified March 9, 2007