Nerve Cells May Set Body Clock

Harvard Medical School researchers have discovered a cluster of nerve cells behind the eyes that are believed to control the body’s circadian rhythms. Down the road, the discovery could result in new therapies for circadian disturbances, such as certain sleep disorders.

The findings were reported in the Dec. 21 issue of Science.

A circadian rhythm is the cycle of daily activity observed in most organisms. The circadian clock itself is an internal mechanism that controls these 24-hour programs, such as the sleep-wake cycle.

“Once we know how it is built, we can follow the pathways out of the brain and investigate how it drives the body’s internal processes, such as the sleep-wake cycle. We’ve only just gotten our foot in the door,” said Associate Professor of Neurobiology Charles J. Weitz ’77, the head of the research team. Although researchers have known about the genes and proteins that cause certain circadian changes, the recent discovery brings to light the actual machinery of the nerve cells, where certain molecular factors are switched on and off to control the daily rhythms.

The chemical factors that control the circadian rhythms work through a receptor known as TGF alpha that then communicates with the nerve cells. The factors regulate daily physical activity, as well as the sleep-wake cycle.

The TGF alpha molecule is not a new discovery—it’s long been known to scientists. But the molecule’s circadian function comes as something of a surprise.

Another surprise: the brain’s pathway to the retina also controls daily activity.

“There was no reason to think that they would converge on the same molecular pathway, but in retrospect, it makes perfect sense. It turns out that certain aspects of the brain are simpler than we thought,” Weitz said.

These findings indicate that the body’s circadian clock can be influenced by outside factors as well as its internal mechanisms.

While there are no immediate applications for the research, new therapies for sleep disturbances probably lie far in the future—there are certainly more directions for the research to take. Weitz plans to look into the other factors by which the clock cells control behaviors.

The circadian factors found by the HMS researchers were identified in a hamster. The findings are strengthened by a separate study that shows that mice with deficient quantities of the receptor do not have normal circadian patterns.

Weitz collaborated with Fred Davis of Northeastern University and Tom Scammell at Beth Israel Deaconess Medical Center on the research. Neither Davis nor Scammell returned calls for comment.