14 July 2003
Temperature, Not Light, Drives Biological Clock
by Kate Melville
Getting over jet lag may be as simple as changing the temperature - your brain temperature, that is.
That's a theory proposed by Erik Herzog of Washington University in St. Louis. Herzog has found that the biological clocks of rats and mice respond directly to temperature changes.
Biological clocks, which drive circadian rhythms, are found in almost every living organism. In mammals, including humans, these clocks are responsible for 24-hour cycles in alertness and hormone levels, for instance. The control panel for these daily rhythms is the suprachiasmatic nucleus (SCN), sometimes called "the brain's Timex." The SCN, located above the roof of the mouth in the hypothalamus, is normally synchronized to local time by light signals carried down the optic nerves. Herzog worked directly with mice SCN cells located in vitro, grown in a dish.
"We found that we can rapidly change the phase of the pacemaker. We can shift its timing to a new time zone," said Herzog. "This paper shows for the first time that we can take control of the clock in a dish. We can tell it what time we want it to think it is."
Herzog's findings were recently published in the Journal of Neurophysiology. His work was funded by the National Institute of Mental Health.
The findings have significant future implications. If brain temperature can be controlled, travellers might never have to deal with jet lag again.
Herzog says that brain temperature is relatively unaffected by environmental temperature, but can be affected by bursts of physical activity, fever, nursing, or a dose of aspirin or melatonin, a drug already used to lessen the effects of jet lag.
In his study, Herzog first needed to establish that the SCN would function normally over a wide range of constant temperatures. He tested the cells in a range from 24 C to 370C. With each change in temperature, the SCN cells continued to operate like clockwork.
"Just like a good watch, the SCN needs to be accurate over a range of temperatures. Your wristwatch would be of no use to you if it sped up every time it became warm. Biological clocks work the same way. Amazingly enough, the SCN can oscillate over a wide range of temperatures."
But Herzog was keeping the cells in constant temperature and, he noted, this is not the way your brain really works. Normally, brain temperature fluctuates by about 1.50C every day. Temperature is at its minimum at daybreak, at its maximum during mid-day. This fluctuation exists even in the absence of any environmental cues, such as light and dark. "If you lived in a cave," Herzog notes, "you'd still have a daily rhythm in temperature.
"So we asked the question if that cycling of temperature, if that 1.5 degrees celsius, would have any effect on the pacemaking of the SCN." As it turned out, the answer was yes.
Herzog simply warmed the isolated SCN during the day and cooled it during the night, reversing the rat's normal daily fluctuation. He found that he could change the time at which the SCN "peaked."
"It shows that the SCN synchronized to the temperature cycle. The temperature cycle entrained it. We fooled the clock by giving it a novel daily schedule, saying 'This isn't the end of the day. This is morning.'"
Herzog's research also sought to disprove the notion put forth in 1998 that shining light on the backs of the knees would be enough to adjust circadian rhythm to a new time zone.
The idea was that by sensing light at the appropriate time people can become synchronized to a new time zone. So Herzog wanted to know: Does the SCN by itself have any light sensitivity?
"We took the SCN out of the animal, put it in a dish, and exposed it to light at night and dark during the day. We asked: does it synchronize to that light-dark schedule? The answer was no." The human biological clock requires the signals from eyes to synchronize to the local light cycle.
Taken together, Herzog's findings indicate that, to avoid jet lag on our next trip to Europe, we should be sure to see the dawn while keeping our brains cool. Future work might lead to a better understanding of what changes brain temperature and why.