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Have Jet Lag? Try VIP Treatment!

During long time evolution, human body developed its own time machine—biological clock. However, the old mechanism is unable to get used to the disordered modern life. When we are on night shifts or travelling across time zones, the biological clock has to adjust to a new time according to light or other environmental stimulus and such process is known as time lag. Recently, researchers at Washington University in St. Louis found a small molecule called VIP and it can help night shift works or travelers to alleviate jet-lag feeling. This research has been published on PNAS.

The master circadian clock in mammals is suprachiasmatic nucleus (SCN), a knot of around 20,000 nerve cells roughly a quarter the size of a grain of rice. Each of the neurons in the SCN is a small biological clock to keep time, however, they are different cells so they have slightly different rhythms. Some of them run a little faster and others a bit slower. In order to produce a consistent circadian rhythms, the cells talk to one another via a molecule called vasoactive intestinal polypeptide (VIP), a small string of amino acids that they receive and release. In other words, cells tell one another what time they think it is through VIP. If you get rid of VIP or its receptor, then the cells would lose synchrony.

 “We were attempting to understand when exactly VIP is released and how it can synchronize the cells.” Says Herzog. However, one of his graduate student discovered that when the amount of VIP was higher than a critical level (100nM), the cells in SCN would desynchronize. The intensity of this effect depends on the doses of VIP, “It’s almost as if at higher doses the cells become blind to the information from their neighbors,” said Herzog.

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High concentration of VIP molecules can impede the circadian rhythms of nerve cells in SCN. (A) Vehicle comparison; (B) 150nM VIP treatment; (C) 100μM VIP treatment. The above raster patterns illustrate the expressions of the biological clock protein PER2 from 20 nerve cells of one SCN over time. Green: expression becomes more; Black: expression becomes less; Yellow: time point of drug treatment. The circles below demonstrates the synchronization of cell biological clock before drug treatment and after. Blue points: the time for the expression of each PER2 to reach the peak. Black arrow: Average vectors of PER2 expression peaks. The length of arrows suggest the synchronization of cell time. *Image source: Sungwon An et al. PNAS. 2013.

However, the researchers then found that temporary desynchronization caused by VIP would not lead to big trouble, instead, it might be useful: when the synchronization between cells was weakened by high doses of VIP, the biological clock re-adjustment became faster. The researchers used mice as experiment subjects and created jet-lag by changing lighting modes. They tested the time for mice to re-adjust biological clock and adapt to the new time. The results showed that the mice gone across eight time zones could accelerate their adaptive process when they were injected with VIP.

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The injection of VIP can accelerate the resetting of mice’ biological clock. When the light-dark schedule was shifted forward by eight hours, corresponding adjustment of spontaneous activity rhythm occurred. The control group, which was injected with human vehicle, needed 7.8 days to adapt the activity rhythm to new light-dark schedule, while the group injected with VIP only needed 4.5 days. *Image source: Sungwon An et al. PNAS. 2013.

This phenomenon is similar to whacking a flickering analog TV to get it to synch or hitting the ceiling near a fluorescent light in hope that its ballast starts to buzz. Comparing to a situation where all cells are in synchronization, cells with disturbed activity rhythm are more sensitive to environmental stimulus and have superior ability of resetting biological clock. A lot of people now live against our biological clocks and research suggests this leads to health issues such as obesity and depression. Although Herzog’s research is still fundamental, his work on VIP is likely to have practical payoffs.

 “This is the first demonstration that giving a bit more of a substance the brain already makes actually enhances the way the circadian system functions.” Herzog said:” We hope 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 light schedule.” Such a treatment may help travelers, shift workers and other who overtax the ability of the biological clock to entrain to environmental cues. But of course, it is absolutely the best to live a life complying with natural time.

Source:EurekAlert!

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