Study Links 'Hunger Hormone' to Memory and Learning

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 Nature Neuroscience, published in the early online edition Feb. 19, 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 co-authored by Stephen Benoit, PhD, and Matthias Tschöp, MD, both of the University of Cincinnati’s 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,” said 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 those 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,” said Dr. Tschöp. “Therefore, we don’t believe we’re dealing with a brain developmental mechanism. Instead, we think we’re looking at the existence of an actual circulating hormone that is required for proper memory performance.”

Connecting this hormone to higher brain functions, said 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,” said 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, of Yale School of Medicine, and supported by the U.S. National Institutes of Health as well as a VA Merit Review grant.

Other co-authors include: Sabrina Diano, Ivaldo da Silva, Ewan Mcnay, Robert Sherwin, and Balazs Horvath, all of Yale School of Medicine; Susan Farr, F. Spencer Gaskin, Naoko Nonaka, Laura Jaeger, William Banks and John Morley, all of St. Louis University School of Medicine; Shirly Pinto, Rockefeller University; Lin Xu and Kelvin Yamada, Washington University School of Medicine; and Mark Sleeman, Regeneron Pharmaceuticals.