Researchers at Yale School of Medicine have found evidence that a hormone produced in the stomach directly stimulates the higher brain functions of spatial learning and memory development, and further suggests that we may learn best on an empty stomach.

Published in the February 19 online issue of Nature Neuroscience by investigators at Yale and other institutes, the study showed that the hormone ghrelin, produced in the stomach and previously associated with growth hormone release and appetite, has a direct, rapid and powerful influence on the hippocampus, a higher brain region critical for learning and memory.

The team, led by Tamas L. Horvath, chair of the Section of Comparative Medicine at Yale School of Medicine and associate professor of comparative medicine, Obstetrics, Gynecology & Reproductive Sciences, and Neurobiology, first observed that peripheral ghrelin can enter the hippocampus and bind to local neurons promoting alterations in connections between nerve cells in mice and rats. Further study of behavior in the animals showed that these changes in brain circuitry are linked to enhanced learning and memory performance.

Because ghrelin is highest in the circulation during the day and when the stomach is empty, these results also indicate that learning may be most effective before meal-time.

“Based on our observations in animal models, a practical recommendation could be that children may benefit from not overeating at breakfast in order to make the most out of their morning hours at school,” said Horvath. “The current obesity epidemic among American school children, which to some degree has been attributed to bad eating habits in the school environment, has been paralleled by a decline of learning performance. It is however too early to speculate if hormonal links between eating and learning are involved in that phenomenon.”

Horvath said that high ghrelin levels or administration of ghrelin-like drugs could also protect against certain forms of dementia, because aging and obesity are associated with a decline in ghrelin levels and an increased incidence of conditions of memory loss like Alzheimer’s disease.

Other authors on the study were first author Sabrina Diano, Susan A. Farr, Stephen C. Benoit, Ewan C. McNay, Ivaldo da Silva, Balazs Horvath, F. Spencer Gaskin, Naoko Nonaka, Laura B. Jaeger, William A. Banks, John E. Morley, Shirly Pinto, Robert S. Sherwin, Lin Xu, Kelvin A. Yamada, Mark W. Sleeman and Matthias H. Tschop.

The study was supported by several grants from the National Institutes of Health and by a VA Merit Review Grant.

Citation: Nature Neuroscience: Online issue, February 19, 2006

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