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Nitric Oxide Levels In Brain Indicate Sleep

Research by investigators from Children's Hospital Boston and the University of Helsinki (Helsinki, Finland), shows that people who must stay awake// all night may be able to put off sleeping if they take care to prevent nitric oxide levels building up in the brain. Previous research had found that nitric oxide production in basal forebrain is needed to produce sleep. Two new papers on the issue are published in the August 18 issue of the Journal of Neurochemistry and the September 5 issue of the European Journal of Neuroscience.

"This understanding of sleep physiology should provide a completely new basis for the development of drugs to prevent excessive sleepiness or to promote sleep," says study co-author Paul Rosenberg, MD, PhD, a researcher in the Neurobiology Program at Children's Hospital Boston, and a physician in the Center for Pediatric Sleep Disorders at Children's and in the Sleep Disorders Center at Beth Israel Deaconess Medical Center.

In 1997, senior investigator Tarja Porkka-Heiskanen MD, PhD, now at the University of Helsinki, first showed that when cats are awake for prolonged periods, a compound called adenosine accumulates in their brains, ultimately producing sleep. Once asleep, adenosine levels gradually decline. Rosenberg had been studying how the brain regulates the accumulation of adenosine in the brain for over 10 years, and, in 2000, he and his colleagues demonstrated in brain cells from rats that adenosine's release is stimulated by nitric oxide. The two teams decided to collaborate.

Studying mildly sleep-deprived rats – kept awake for an extra three hours – they found that nitric oxide production in the basal forebrain, but not in other parts of the brain, increased, by 50 to 150 percent. When they injected compounds that inhibit nitric oxide production into this region of the brain, adenosine levels did not increase and sleep was completely abolished (one type of inhibitor abolished dreaming, or REM,
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