Scientist discovers way to control internal clock

© Thinkstock

Forget those hi-tech apps and widgets. Forget your anachronistic lo-tech paper calendars with cutesy pictures of animals or romantic misty landscapes. You might react to these artificial cues and bring some semblance of order to your life, but physiologically, your body dances to a different tune - the hard-wired circadian rhythms that drive many biological processes to cycle every 24 hours.

From the very beginnings of life on earth, in the earliest cells of the most primitive organisms, this fundamental process of life has been essential for survival. To protect the all-important replicating DNA of the first living beings from high ultraviolet radiation during the daytime, those organisms developed photosensitive proteins and circadian rhythms. Surviving to this day, for instance, the fungus retains this clock-regulated mechanism.

When the natural function of circadian rhythm is disrupted, the human body can succumb to many related health problems, including metabolic disease and neuropsychiatric illnesses such as bipolar disorder, anxiety, depression, schizophrenia, as well as sleep and anxiety disorders. You mess with that pre-fungal bio-app, the circadian clock, at your peril.

But some intriguing work by Thomas Burris, Ph.D., chair of pharmacological and physiological science at Saint Louis University (SLU) and his colleagues brings promise of new ways to treat problems that are associated with circadian dysfunction.

Burris's research has been published in the journal and includes intriguing findings about a small molecule, called REV-ERB, that directs the activity of key "clock proteins" and offers the potential to manage circadian rhythm and treat those disorders which result from its disruption.

REV-ERB appears to play a key role in regulating mammals' internal clocks. "It has been suggested that REV-ERB is a core component of our clock," said Burris. "Mice without it are arrhythmic. This study demonstrated that when we give mice a synthetic compound that turns REV-ERB on, it altered their circadian rhythm."

When the researchers examined the effects of the REV-ERB drug on patterns of sleep and wakefulness, they discovered that the compound increases wakefulness, reduces REM and slow-wave sleep, and, perhaps most importantly, it can reduce anxiety.

The potential of REV-ERB as a treatment is enormous because it appears to act in a totally different way from current medications. Many commonly prescribed drugs such as cocaine and amphetamines, which increase arousal, or "wakefulness", unfortunately lead to increased anxiety. Conversely, drugs like benzodiazepines and ethanol which lower anxiety also decrease arousal. REV-ERB, however, seems to control the clock in a way that is distinct from these common pathways.

Another benefit of REV-ERB is that the drug may suppress reward-seeking behavior. Previous research has shown that there is a circadian component associated with drug addiction. In experiments with mice, mutations in the "clock genes" which affect internal clocks altered responsivity to rewards associated with cocaine, morphine and alcohol. If Burris's theories are correct, treatment with REV-ERB could modulate reward-seeking behavior, and so may be useful in treating addiction as well as sleep and anxiety disorders.