ScienceDaily (Oct. 26, 2009) — Anyone who has pulled an all-nighter or flown across an ocean knows you can’t mess up your sleep schedule without unpleasant consequences. New research in mice now shows that throwing off natural circadian rhythms over the long term can seriously disturb the body and brain, causing weight gain and impulsive behavior. It seems even to make mice dumber, or at least slower at solving new mazes.

A new study has found that chronic disruption of one of the most basic circadian (daily) rhythms -- the day/night cycle -- leads to weight gain, impulsivity, slower thinking, and other physiological and behavioral changes in mice, similar to those observed in people who experience shift work or jet lag.

The research, presented at Neuroscience 2009, the annual meeting of the Society for Neuroscience is helping scientists better understand the neurobiological mechanisms behind circadian disruptions.

"Our findings have implications for humans," said lead author Ilia Karatsoreos, PhD, of Rockefeller University. "In our modern industrialized society, the disruption of our individual circadian rhythms has become commonplace, from shift work and jet lag to the constant presence of electric lighting. These disruptions are not only a nuisance, they can also lead to serious health and safety problems," he said.

Karatsoreos and his colleagues housed the animals in a day/night cycle of 20 hours (10 hours of light and 10 hours of dark), rather than the roughly 24-hour cycle to which the animals' internal brain and body clocks are normally set. After six to eight weeks, the mice exhibited numerous physiological changes not seen in a control group.

While not any more active than the control mice, the disrupted mice were impulsive, a behavior measured in part by how long they wait to emerge into the light from a dark compartment in a cage. They were slower to figure out changes made to a water maze they had mastered, suggesting reduced mental flexibility. Physically, their body temperature cycles were disorganized when compared to their peers and the levels of hormones related to metabolism, such as leptin, which regulates appetite, and insulin, were elevated. Consequently the mice gained weight even though they were fed the same diet as the controls.

The researchers also found that the brains of the disrupted mice had shrunken and less complex neurons in the medial prefrontal cortex, an area important to the so-called executive function, which regulates mental flexibility among other things. “Those changes may help explain some of the behavioral effects of circadian disruptions,” Karatsoreos says.

Research was supported by Canadian Institutes of Health Research, the National Institute of Mental Health, and Sepracor.

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The above story is reprinted from materials provided by Society for Neuroscience.

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Night and day. Experiments with mice, such as one in which scientists gauge the rodents' willingness to venture from a dark compartment to a bright one, show that disrupting circadian rhythms has a pronounced impact on behavior and physiology. (Credit: Image courtesy of Rockefeller University)

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