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July 12, 2005

Mood Lighting: Penn Researchers Determine Role Of Serotonin In Modulating Circadian Rhythm

Topics: General Science

Interest in circadian rhythm isn't just among the jet set trying to adjust to jet lag, anymore. There is now increasing evidence to suggest that the administration of cytotoxic agents, at the appropriate circadian phase, can significantly increase the therapeutic index of current cancer therapies.

- Science Daily (thanks to Debra)
Researchers at the University of Pennsylvania School of Medicine have determined how serotonin decreases the body's sensitivity to light and that exposure to constant darkness leads to a decrease in serotonin levels in the brain of fruit flies. These findings suggest that serotonin may play a role in maintaining circadian rhythm, as well as modulating light-related disorders such as seasonal affective disorder (SAD). Senior author Amita Sehgal, PhD, Professor of Neuroscience at Penn and a Howard Hughes Medical Institute (HHMI) Investigator, and colleagues report their findings in the July 7 issue of Neuron.
The body's 24-hour (circadian) clock controls cycles of wakefulness and sleep, as well as the rhythm of other physiological functions, such as body temperature and blood pressure. Although the body functions on roughly a 24-hour schedule, this cycle is capable of being reset by environmental disturbances. In Sehgal's lab, fruit flies provide the model system for examining entrainment, the synchronization of the internal clock to the environment.

"In humans, a light pulse in the early evening delays rhythm-if it stays light later, you stay up later," says Sehgal. "Disturbances in the late evening advance the body clock-an early dawn leads to an early rise."

Entrainment was tested in flies by exposing them to a pulse of light during the dark period. Closely resembling the body clock adjustment seen in humans, Sehgal's flies reset their body clock following the "night-time" disturbances. However, this adjustment was lessened when the flies were treated with serotonin prior to the test.

Sehgal speculates that serotonin is acting to protect the body clock from being over-responsive to light disturbances. "You do not want your clock to be so supersensitive to light that small fluctuations are going to throw it out of whack," she explains. "Serotonin appears to modulate the response of the body clock to light."

Proposed model for the effect of serotonin molecular signaling in fruitfly clock cells. Serotonin binds to its receptor, d5-HT1B, setting off a cascade of events within the cell that involves the clock proteins SGG, TIM, PER, and CRY, and governs the fly's circadian response to light. Alternations in the level of the serotonin receptor affects molecular and behavioral responses of the fly to light. (Credit: Amita Sehgal, University of Pennsylvania School of Medicine and Cell Press)

Read the entire article ...

Posted by Hyscience at July 12, 2005 12:15 AM

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