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March 2006 Issue

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'Hunger Hormone' Linked to Memory and Learning

Published March 2006

A hormone that regulates food intake and body weight could be involved in processes leading to memory loss associated with aging and Alzheimer's disease.

Research appearing in the March 2006 edition of Nature Neuroscience shows that the stomach hormone ghrelin directly influences activity and plasticity of a brain region associated with learning and memory.

The study, led by Yale School of Medicine, was coauthored by Stephen Benoit, PhD, and Matthias Tschöp, MD, both of the psychiatry department and the Obesity Research Center at UC's Genome Research Institute.

In 2000, Dr. Tschöp's group was the first to link ghrelin to increased hunger, appetite, body weight and obesity.

"We know that blood levels of ghrelin are highest prior to mealtime, or on an empty stomach," says Dr. Tschöp. "These levels decrease after each meal and are significantly lower in obese individuals."

Impressed by observations indicating that this "hunger hormone" might also boost memory performance, the scientists went on to compare the behavior of animals with normal levels of ghrelin to those with the ghrelin-producing gene "knocked out."

They found that animals without a ghrelin-producing gene performed significantly worse in a variety of behavioral tests--suggesting that ghrelin might play a role in higher brain function.

The researchers confirmed that ghrelin actually binds to its receptor and activates neurons in the hippocampus, the brain region responsible for learning and memory performance.

"When we put animals without the gene on ghrelin replacement therapy, we were able to rapidly restore the memory and learning behaviors on which they had performed so poorly," says Dr. Tschöp.

"Therefore, we don't believe we're dealing with a brain developmental mechanism," he says. "Instead, we think we're looking at the existence of an actual circulating hormone that's required for proper memory performance."

Connecting this hormone to higher brain functions, says Dr. Benoit, could offer insight into memory loss associated with obesity, aging and Alzheimer's.

"Previous studies have shown a higher incidence of Alzheimer's disease among obese patients," says Dr. Benoit. "Our data suggests that high ghrelin levels, achieved by dietary changes or through ghrelin-like drugs, could potentially protect us from memory loss associated with both aging and obesity."

The study was led by Tamas Horvath, PhD, of Yale School of Medicine, and supported by the U.S. National Institutes of Health and a Veterans Affairs Merit Review grant.

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