Researher’s Discover Food Related Clock in the Brain

In investigating the intricacies of the body’s biological rhythms, scientists at Beth Israel Deaconess Medical Center (BIDMC) have discovered the existence of a “food-related clock” which can supersede the “light-based” master clock that serves as the body’s primary timekeeper. The findings, which appear in the May 23 issue of the journal Science, help explain how animals adapt their circadian rhythms in order to avoid starvation, and suggest that by adjusting eating schedules, humans too can better cope with changes in time zones and nighttime schedules that leave them feeling groggy and jet-lagged.

“For a small mammal, finding food on a daily basis is a critical mission,” explains the study’s senior author Clifford Saper, MD, PhD, Chairman of the Department of Neurology at BIDMC and James Jackson Putnam Professor of Neurology at Harvard Medical School. “Even a few days of starvation is a common threat in natural environments and may result in the animal’s death.”

The suprachiasmatic nucleus (SCN), a group of cells in the brain’s hypothalamus, serves as the body’s primary biological clock. The SCN receives signals about the light-dark cycle through the visual system, and passes that information along to another cell group in the hypothalamus known as the dorsomedial nucleus (DMH). The DMH then organizes sleep-wake cycles, as well as cycles of activity, feeding and hormones.

“When food is readily available,” explains Saper, “this system works extremely well. Light signals from the retina help establish the animals’ circadian rhythms to the standard day-night cycle.” But, if food is not available during the normal wake period, animals need to be able to adapt to food that is available when they are ordinarily asleep.

In order to survive, animals appear to have developed a secondary “food-related” master clock. “This new timepiece enables animals to switch their sleep and wake schedules in order to maximize their opportunity of finding food,” notes Saper, who together with lead author Patrick Fuller, PhD, HMS Instructor in Neurology and coauthor Jun Lu, MD, PhD, HMS Assistant Professor of Neurology, set out to determine exactly where this clock was located.

“In addition to the oscillator cells in the SCN, there are other oscillator cells in the brain as well as in peripheral tissues like the stomach and liver that contribute to the development of animals’ food-based circadian rhythms,” says Saper. “Dissecting this large intertwined system posed a challenge.”

To overcome this obstacle, the authors used a genetically arrhythmic mouse in which one of the key genes for the biological clock, BMAL1, was disabled. They next placed the gene for BMAL1 into a viral vector which enabled them to restore a functional biological clock to only one spot in the brain at a time. Through this step-by-step analysis, the authors uncovered the feeding entrained clock in the DMH.

“We discovered that a single cycle of starvation followed by refeeding turns on the clock, so that it effectively overrides the suprachiasmatic nucleus and hijacks all of the circadian rhythms onto a new time zone that corresponds with food availability,” says Saper. And, he adds, the implications for travelers and shift workers are promising.

“Modern day humans may be able to use these findings in an adaptive way. If, for example, you are traveling from the U.S. to Japan, you are forced to adjust to an 11-hour time difference,” he notes. “Because the body’s biological clock can only shift a small amount each day, it takes the average person about a week to adjust to the new time zone. And, by then, it’s often time to turn around and come home.”

But, he adds, by adapting eating schedules, a traveler might be able to engage his second “feeding” clock and adjust more quickly to the new time zone.

“A period of fasting with no food at all for about 16 hours is enough to engage this new clock,” says Saper. “So, in this case, simply avoiding any food on the plane, and then eating as soon as you land, should help you to adjust – and avoid some of the uncomfortable feelings of jet lag.”

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Article adapted by MD Only from original press release.
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Contact: Bonnie Prescott>
Beth Israel Deaconess Medical Center

Natural compound in chocolate boost memory…

May help protect against cognitive decline in aging

A natural compound found in blueberries, tea, grapes, and cocoa enhances memory in mice, according to newly published research. This effect increased further when mice also exercised regularly.

“This finding is an important advance because it identifies a single natural chemical with memory-enhancing effects, suggesting that it may be possible to optimize brain function by combining exercise and dietary supplementation,” says Mark Mattson, PhD, at the National Institute on Aging.

The compound, epicatechin, is one of a group of chemicals known as flavonols and has been shown previously to improve cardiovascular function in people and increase blood flow in the brain. Flavonols are found in some chocolate. Henriette van Praag, PhD, of the Salk Institute, and colleagues there and at Mars, Inc., showed that the combination of exercise and a diet with epicatechin also promoted structural and functional changes in the dentate gyrus, a part of the brain involved in the formation of learning and memory. The findings, published in the May 30 issue of The Journal of Neuroscience, suggest that a diet rich in flavonols may help reduce the incidence or severity of neurodegenerative disease or cognitive disorders related to aging.

Van Praag and her team compared mice fed a typical diet with those fed a diet supplemented with epicatechin. Half the mice in each group were allowed to run on a wheel for two hours each day. After a month, the mice were trained to find a platform hidden in a pool of water. Those that both exercised and ate the epicatechin diet remembered the location of the platform longer than the other mice.

When studying their brains, van Praag and her colleagues found that these mice had greater blood vessel growth in the dentate gyrus and had developed more mature nerve cells, suggesting an enhanced ability of the cells to communicate. Further analysis showed that the epicatechin and exercise combination had a beneficial effect on the expression of genes important for learning and memory, and decreased the activity of genes playing a role in inflammation and neurodegeneration.

The researchers found that sedentary mice fed epicatechin showed enhanced memory, blood vessel growth, and gene activity, but these benefits were even more evident in mice that also exercised.

“A logical next step will be to study the effects of epicatechin on memory and brain blood flow in aged animals,” says van Praag, “and then humans, combined with mild exercise.”

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Article adapted by MD Only Weblog from original press release.
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The work was a supported by a grant from the US Defense Department’s Defense Advanced Research Projects Agency. Mars, which markets a flavonol-rich line of chocolate, supplied the epicatechin.

The Journal of Neuroscience is published by the Society for Neuroscience, an organization of more than 36,500 basic scientists and clinicians who study the brain and nervous system. Van Praag can be reached at vanpraag@salk.edu.

Contact: Sara Harris
Society for Neuroscience