Artificially separated from a natural cycle of light and dark, the bodies and brains of mice go haywire in ways that may mimic the human effects of circadian disruption.

The mice are not an analogue for humans who work a night shift or regularly travel across multiple time zones, but they could provide a model for deeper investigations of what happens when circadian rhythms are bumped.

After all, it's only been a century since mechanized timekeeping and artificial lighting made it possible to override a biological system calibrated for the last several billion years, with circadian systems found in even the most primitive algae.

"Modern society has resulted in a round-the-clock lifestyle, in which natural connections between rest-activity cycles and environmental light-dark cycles have been degraded or even broken," wrote researchers led by neuroscientist Bruce McEwen of Rockefeller University in a Dec. 11 Proceedings of the National Academy of Sciences study. "However, the ramifications of chronic disruption of the circadian clock for mental and physical health are not understood."

Yet if the effects are not understood in exact detail, a growing body of evidence points to problems. Circadian "clock genes," centrally controlled in mammals by a brain region that gets signals straight from the retina, have central regulatory roles in gene networks. Hormone-balance signals are tied to circadian cycles, and night-shift work has been correlated with increases in diabetes, heart disease and cancer.

Such correlations can flag a problem but don't say much about how it works, sending researchers to work on animals. To create chronic circadian disturbance, McEwen's team turned lab lights on and off to create 20-hour days for mice, while a control group was kept on a regular 24 hour schedule. Within six weeks, the disrupted group started to gain weight, despite eating the same diet as controls. They grew obese, and had altered levels of insulin and leptin, two key metabolic hormones.

Effects extended to their brains. In the prelimbic prefrontal cortex, a region important to emotional control and cognitive flexibility, neurons shrank and were arranged in less complex ways. The mice had trouble learning to navigate mazes, and were spooked by new environments.

The researchers hope their model of disruption will be used by other scientists to conduct further investigations of circadian disruption.

The findings demonstrate "the central role circadian rhythms play in both mental and physical health," they wrote. "How these findings translate to humans is an important area of research, because such effects could put chronically disrupted individuals at risk for developing metabolic and cardiovascular problems."

Images: 1) Richard Winchell/Flickr. 2) Weight gain and metabolic hormone levels in circadian-normal and circadian-disrupted mice./PNAS.

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Citation: "Disruption of circadian clocks has ramifications for metabolism, brain, and behavior." By Ilia N. Karatsoreos, Sarah Bhagat, Erik B. Bloss, John H. Morrison, and Bruce S. McEwen. Proceedings of the National Academy of Sciences, Vol. 108 No. 2, Jan. 5, 2011.