New brain protein regulates sleep and anxiety

Findings point to a different way to treat sleep disorders and anxiety

UC Irvine pharmacology researchers have found how a recently discovered brain protein plays a major role regulating sleep and stress – a discovery that can lead to a new class of drugs for treating ailments ranging from sleep and anxiety disorders to attention deficit disorder.

The UCI team conducted tests to see how neuropeptide S (NPS) affected behavioral responses in rodents. They found that NPS increases alertness, suppresses sleep and even controls stress responses. This establishes NPS, which was first discovered in 2002, as an important modulator of sleep and alertness. This study also suggests NPS has potential as a target for new drugs to treat sleep disorders. The study appears in the Aug. 19 issue of Neuron.

“Since our knowledge of NPS is so new, we may be at the tip of the iceberg in understanding its function,” said Rainer Reinscheid, assistant adjunct professor in pharmacology and lead researcher in the study. “We’ve found NPS to be so active with sleep and anxiety behavior that it can be a very attractive drug target, both to enhance and to suppress its function.”

In testing how NPS is involved with both sleep regulation and stress behaviors, the researchers found that NPS is produced by previously unidentified neurons in a brain stem region known for regulating arousal and anxiety. Further tests demonstrated that rats injected with NPS showed increased alertness and reduced slow-wave and REM sleep over untreated rats.

NPS receptor proteins were also detected in stress-related brain regions such as the amygdala and thalamus. In behavior tests that measure their stress-related anxiety, mice injected with NPS show fewer anxiety responses and increased activity than untreated mice. Sleep and fatigue are in a balance – insufficient sleep will increase fatigue, and only sleeping can reduce fatigue. There is a variety of sleep and fatigue disorders, which range from the most severe affecting only a set of individuals to mild ones nearly everyone will encounter.

The most severe form of sleep disorder is narcolepsy, in which affected individuals suffer from irresistible sleep attacks. Most common is the excessive daytime sleepiness that may result from chronic sleep deprivation or sleep impairments. Very little is known about the basic mechanisms that regulate these physiological responses, but the UCI study provides a first glance at a neuropeptide that affects these sleep mechanisms.

“Some 100,000 Americans are currently treated for excessive daytime sleepiness, but the number of the undiagnosed is far larger,” said study co-author Olivier Civelli, the Eric L. and Lila D. Nelson Chair in Neuropharmacology at UCI. “Furthermore, symptoms of sleepiness, often recognized as fatigue, are associated with numerous other illnesses, such as multiple sclerosis, Parkinson’s disease and also depression. If it can be shown that the NPS system is a major modulator of fatigue, then its therapeutic potentials will be immense.”