Disrupting sleep causes problems for the body and brain

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.

Rockefeller University postdoctoral fellow Ilia Karatsoreos, who led the research, says the implications for humans are significant. “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, but can also lead to serious health and safety problems.” Karatsoreos, who works in Bruce S. McEwen’s Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, presented his findings October 19 in Chicago as part of a panel at Neuroscience 2009, the Society for Neuroscience’s annual meeting.

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.

To test the neurological impact of disrupting circadian rhythms, Karatsoreos and colleagues adjusted the hours in which mice were exposed to light, from their natural 24-hour cycle to 20 hours, with 10 hours of light and 10 hours of dark. After six to eight weeks of these shortened days, these mice began acting differently than their peers in a control group. They also showed several physiological differences.

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.

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