Gut hormone ghrelin (bottom) increases synapse density (arrowheads) and improves memory.
HORVATH/MACMILLAN
The growling stomach produces the hormone ghrelin, which stimulates fat storage and appetite by binding neurons in the hypothalamus. But ghrelin also binds neurons in the hippocampus—a center for forming memories.
Horvath's team shows that ghrelin's hippocampal action promotes long-term potentiation and a higher synaptic density in the CA1 region of the hippocampus. Both characteristics correlated with improved spatial memory and learning.
The authors injected rodents with ghrelin and used three behavioral tests that rely on hippocampal memory functions—exploring different arms of a plus-shaped maze and two foot-shock avoidance tests. In each, ghrelin improved memory performance in a dose-dependent manner. Performance was improved 20–30% at the highest dose, effectively turning C-grade mice into straight-A students. In a final test, ghrelin knockout mice showed little ability to recognize a novel object unless they got a shot of ghrelin.
Aged SAMP8 mice—a model for Alzheimer's disease—also showed improved memory performance with ghrelin dosing, and the authors propose ghrelin analogues as potential treatments for memory loss. Of course, over-eating and weight gain would be potential side effects.
Horvath says ghrelin represents a primitive system in which a gut hormone acts directly on the higher brain to change synaptic plasticity, and affect cognition. “If you are hungry, you need to be alert and aware of your environment,” for example to help in finding the next meal. His group now plans to look for the same mechanism in humans.
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