A new study in mice finds that at high doses, VIP, a molecule that normally synchronizes biological clock cells in the brain, knocks them out of synch, allowing them to reset quickly to a new light-dark cycle.
The researchers – from Washington University in St. Louis, MO, and the University of California, Santa Barbara – suggest the finding may help develop treatments for sleep problems brought on by jet lag and shift work.
In a recent issue of the Proceedings of the National Academy of Sciences (PNAS), they explain how desynchronized neurons took only half as long as undisturbed brain cells to entrain to a new light-dark cycle.
In mammals, the master biological clock is a cluster of 20,000 neurons that form the suprachiasmatic nucleus (SCN) – a knot of brain tissue about the size of a grain of rice, which in humans sits on the brain’s midline.
Each brain cell in the SCN keeps time, but being individual cells, they have different rhythms.
However, they seem to tell each other about their individual timekeeping using a molecule called VIP (vasoactive intestinal polypeptide), which helps them stay synchronized, as Erik Herzog, a professor of biology in Arts & Sciences at Washington University, explains:
“They’re like a society where each cell has its own opinion on what time of day it is. They need to agree on the time of day in order to coordinate daily rhythms in alertness and metabolism.”
He says if you get rid of VIP or the receptor for VIP, the cells fall out of step with each other.
But as the researchers were trying to discover exactly how VIP works to synchronize cells, they found to their surprise that with too much VIP, the cells become desynchronized. And the more VIP that was released, the more desynchronized they became.
Prof. Herzog explains:
“It’s almost as if at higher doses the cells become blind to the information from their neighbors.”
At this point, they formed a hunch that perhaps this might make the system more sensitive to environmental cues.
They were encouraged to think this because meanwhile, at Santa Barbara, co-author and chemical engineer Linda Petzold and colleagues had developed a numerical model that predicted increasing VIP would lead to “phase tumbling” or loss of synchrony and accelerated entrainment.
Prof. Herzog says being able to adjust quickly to environmental cues is important because the master clock has evolved to adjust slowly to seasonal changes in light-dark cycles, not the much more abrupt changes that characterize modern life.
Even a 1-hour shift, like daylight-saving patterns, are known to increase the risk of fatal traffic accidents and heart attacks.
He explains that by using lab mice, they tested the effect of adding extra VIP:
“We found that in mice we could cut ‘jet lag‘ in half by giving them a shot of VIP the day before we ‘flew them to a new time zone,’ by shifting their light schedule.”
The study is the first to show that a chemical naturally present in the brain can improve the function of the circadian system.
The researchers now want to focus on a way to exploit this as an avenue for new treatments.
Prof. Herzog adds:
“We’re hoping we’ll be able to find a way to coax the brain into releasing its own stores of VIP or a light trigger or other signal that mimics the effects of VIP.”
A study published in the journal Obesity earlier this year found that the body’s biological clock increases evening time hunger and cravings for sweet, starchy and salty foods.