Body Temperature May Be Regulated by Neural Connection between the Retina and the "Body Clock," UB Scientists Find

BUFFALO, N.Y. -- Scientists from the University at Buffalo School of Medicine and Biomedical Sciences are helping to reveal the mysteries of the mammalian biological clock, the grouping of cells in the brain that regulates the basic physiological functions known as circadian rhythms.

Presenting today (April 13) at the Experimental Biological meeting in San Diego, UB researchers report that one of the important circadian rhythms, the daily fluctuations in body temperature, is governed in part by neuronal circuits that link light-sensitive receptors in the retina with the hypothalamus. The mammalian "clock works," called the suprachiasmatic nucleus, is located in this brain structure.

The researchers report also that these circuits cease to work properly when the animals experience low-oxygen levels, and that the return of normal body temperature rhythm when oxygen is restored depends on the type of stimulation received by these retinal receptors. Unlike rods and cones, the retinal receptors responsible for vision, these recently discovered receptors inform the brain about the amount of light in the environment.

"This research is a wonderful way to find out the effect of the neural interactions among brain regions," said Beverly Bishop, Ph.D., SUNY Distinguished Teaching Professor in the UB Department of Physiology and Biophysics and lead author on the study. "Only when we know what functions are under the clock's neural control will we understand conditions such as sleep apnea, which induces intermittent hypoxia, insomnia, SIDS (sudden infant death syndrome) and high altitude mountain sickness. Understanding how circadian rhythms regulate body functions and behaviors has extremely broad implications."

Bishop added, "We know a lot about the particular cells comprising the suprachiasmatic nucleus, the 'body clock,' and the genetic control of the proteins they produce. What isn't understood is how this remarkable group of cells imposes its rhythms on other cell groups throughout the body.

"Systems physiologists can contribute to the field by determining the neurohormonal interactions between the 'clock' and the complex systems controlling body temperature and motor activity," she said. "We already have made several key contributions to the understanding of the clock's interaction with other brain regions."

The present study, using rats as an animal model, was designed to determine the effect of an environment of constant darkness on the circadian rhythm of body temperature in rats and the body temperature response during low oxygen levels, or hypoxia, under this condition.

These results were compared with those reported during 12-hour day-light cycles and constant light. To collect the data, rats fitted with a miniature temperature probe were subjected to seven days of constant darkness in a room temperature of 21 degrees Centigrade (70 degrees Fahrenheit.). Body temperature was recorded every 6 minutes for three days on room air, three days on 10 percent oxygen in nitrogen (hypoxia), followed by 11 days on air.

Results showed that in constant darkness before hypoxia, the rats maintained a "robust" temperature circadian rhythm around a set point of 99 degrees Fahrenheit. At the onset of hypoxia, the circadian rhythm disappeared and temperature dropped to around 91 degrees Fahrenheit, before slowly rising toward its pre-hypoxic mean.

When normal oxygen was restored, body temperature promptly returned to its original set point, but circadian regulation did not return for another three or four days, results showed.

When rats underwent the same experimental procedures during 12-hour light/dark cycles and during constant light, body temperature response during and after hypoxia differed, Bishop said. During light/dark conditions, the temperature response during hypoxia was similar, but circadian rhythm returned immediately when normal oxygen was restored.

During hypoxic conditions under constant light, temperature again fell in response to hypoxia as in the other conditions, results showed, but its rise toward normal during hypoxia was delayed for 24 hours before rising at a slow rate. When normal oxygen was restored, circadian rhythm returned in around three days.

These findings show that hypoxia stops the biological clock, Bishop said. "We find that the input from retinohypothalmic neural tract strongly influences daily temperature oscillations, the magnitude and time course of the response induced by hypoxia, and the amount of time required for circadian rhythm to return after hypoxia," she said.

Additional researchers contributing to the study were John Krasney, Ph.D., UB professor of physiology and biophysics, and Daniel Rifkin, M.D., UB assistant professor of neurology and director of the Sleep Disorder Center of Western New York. Students Joseph Augustin and Sherria Lewis also were involved in the research.

The study was supported by a grant from the American Lung Association.