Photograph by Jim Richardson, Corbis

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Airplanes have opened up a world of convenience for globe-trotters. But there is a price: jet lag.

Photograph by Jim Richardson, Corbis

Jet Lag Cure for Mice Illuminates Inner Workings of Circadian Clocks

The hormone vasopressin could be key to unlocking the treatment of jet lag, says new study.

Leaving on a jet plane usually means you're either off on an adventure or coming home to familiar things. It also means you'll probably have to deal with jet lag.

That exhausted, disoriented feeling is your body's way of telling you that it thinks it's the wrong time of day. And usually, you just have to suffer through it until your body adjusts to the new time zone. (Related: "Is Your Brain Sleeping While You're Awake?")

But a new study in the journal Science finds that interfering with a hormone in mammalian brains called vasopressin could be the key to quickly resetting our internal clock without having to suffer through jet lag.

Vasopressin's better-known function is to control the body's fluid balance by regulating how much water we excrete in our urine. But it turns out that it's also the currency for communication between cells in a certain part of the brain called the suprachiasmatic nucleus (SCN).

The SCN is the "master clock" in our bodies, regulating our daily rhythms, said study co-author Hitoshi Okamura, who specializes in mammalian circadian systems at Kyoto University in Japan. He likens the SCN to the conductor of an orchestra, and the structure is found only in mammals. (Related: "Marine Animals Keep Time With Multiple Clocks.")

No one quite knows how the SCN orchestrates the body's daily rhythms, Okamura said. But since vasopressin seemed to be a key component of the communication network between SCN neurons, he decided to see what would happen if that vasopressin network was disrupted.

Inducing Jet Lag

Okamura and colleagues took two populations of mice—one with functioning vasopressin receptors and a second population missing two of the hormone's key receptors—and put them on a 12-hour dark and 12-hour light cycle for two weeks.

Then the researchers advanced the light-dark cycle by eight hours and recorded how long it took the mice in both populations to adjust to their new schedules.

The "intact," or normal, mice took about eight to ten days to get over their jet lag and settle into the new light-dark cycle. But the mice missing their vasopressin receptors needed only two to four days to adjust.

To confirm that missing vasopressin receptors were responsible for the quick adjustment—and not some other factor like a developmental abnormality in the mice missing receptors—researchers used drugs to block vasopressin receptors in intact mice.

They induced jet lag in the treated mice and found that they were also able to adjust quickly to their new light-dark schedule.

Predicting Airplanes

These results seem to indicate that vasopressin is responsible for keeping the body's circadian clock on track, said Okamura. And it is very good at its job.

He speculates that a strong clock able to resist resetting every time a full moon happened, or a wildfire lit up the night sky, would have been crucial for ancient mammals living a nocturnal life. (Related: "Blame Bad Night's Sleep on the Moon.")

But what was advantageous for the ancestors of modern-day mammals has led to problems for people living in the here and now. "Evolution [did] not predict the appearance of [the] airplane," said Okamura.

Since vasopressin neurons are also present in the human SCN, it's possible that people have a similar vasopressin receptor system to the one researchers studied in mice, he added.

"Our findings pave the road to perform pharmacological intervention for shift worker–related diseases, including hypertension, metabolic syndrome, and cancer," Okamura said.

Some studies have shown that a disruption of melatonin production at night—which would occur in people working the night shift for decades—could lead to increased risks of certain cancers like breast cancer.

A Multipurpose Hormone

"I think it's an excellent study," said Michael Gorman, a neuroscientist from the Center for Chronobiology at the University of California, San Diego.

"Basically, the upshot of it is that it really gives hope that we could be able to shift the clocks of humans in a much more rapid and direct fashion than many people might expect," he added.

But the neuroscientist—who was not involved in the study—also warns that the development of a drug might not be as straightforward as some would hope.

"One wants to be cautious because vasopressin does other things than help the clock work. It's involved in blood pressure and fluid balance," he explained. "[And] these receptors are implicated in behavior like aggression and spatial learning."

Despite these challenges, now that we know vasopressin is part of this clock mechanism, researchers could look at the hormone's upstream or downstream effects and manipulate those to give folks some relief, rather than try to manipulate the hormone itself, Gorman said.

Jet lag affects many systems in the body, not just a person's sleep-wake cycle, he added. "Your stomach may be on a different time zone, and your kidneys may be on a different time zone from your stomach, [while] your sleep-wake cycle may be on a time zone in between."

Any solution to such a complex phenomenon won't come easy.

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