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Could the ‘hunger hormone’ boost memory?

Brain-gut axis
University of Southern California scientists suggest ghrelin, known for its role in regulating appetite, may also be important for memory control. (Enterin)

Ghrelin is often called the “hunger hormone” because it regulates appetite. A team of researchers at the University of Southern California (USC) has identified a potential new role for the hormone: promoting memory.

After the researchers blocked ghrelin signaling in rats, they observed that the animals showed signs of impaired memory, they reported at the annual meeting of the Society for the Study of Ingestive Behavior. That led the USC team to hypothesize that ghrelin may also help control memory.

Ghrelin is produced mainly in the stomach and binds to receptors on the vagus nerve, which connects the brain with major organs, including those in the digestive tract. Vagus nerve stimulation has been shown to enhance memory, and Scott Kanoski and colleagues at USC recently found that the vagus nerve influences memory functions that depend on the brain’s hippocampus.

For the new study, Kanoski’s team blocked the ghrelin communication pathway in the rats’ vagus nerve by using RNA interference to tamp down ghrelin receptors. The rodents were then given a series of memory tasks.

According to the researchers, rats with reduced ghrelin signaling performed poorly in a test of episodic memory, a hippocampus-dependent process that involves remembering details of past personal experiences such as when and where particular events happened.

What’s more, when the ghrelin signal was impaired, the animals ate more frequently but in smaller amounts with each meal. The researchers attributed the change in eating habits to episodic memory problems.

“Deciding to eat or not to eat is influenced by the memory of the previous meal,” said Elizabeth Davis, the study’s first author, in a statement. “Ghrelin signaling to the vagus nerve may be a shared molecular link between remembering a past meal and the hunger signals that are generated in anticipation of the next meal.”

Ghrelin and its receptor have been linked to a variety of biological processes including gastrointestinal activities, glucose metabolism, inflammation and neurological disorders such as seizures and depression. But efforts to target it for therapeutics have yielded mixed results.

For example, Allergan is developing relamorelin, a ghrelin agonist, for the treatment of diabetic gastroparesis. Allergan acquired the drug when it bought Motus Therapeutics in 2016, even though the data from a phase 2b trial weren’t very convincing. Michigan-based Millendo Therapeutics, which acquired French endocrinology specialist Alizé Pharma in 2017, just started pivotal trials of livoletide (AZP-531), an analog of unacylated ghrelin, in patients with the hunger disorder Prader-Willi syndrome.

The USC scientists’ new findings provide some further insight into the relationship between episodic memory and ghrelin. Future studies could examine the potential for improving memory in people by manipulating ghrelin signaling from the gut to the brain, the team said.