A simple energy molecule gives female mice a memory boost

Acetate facilitates long-term memory. Credit: Science Signaling (2026). DOI: 10.1126/scisignal.aec0496

A team of scientists from the U.S. has discovered that acetate, a simple molecule involved in how our bodies create energy, can significantly increase long-term memory in female mice. The researchers were looking for a direct link between metabolism and memory, specifically, how the fuels our bodies use (like acetate) can change the way our brain cells work.

The scientists injected acetate into adult male and female mice to see how it travels from the bloodstream to the brain to cause changes in behavior. They also wanted to see whether this molecule affected the sexes in different ways. A control group was given a saline solution.

Memory tests

Then, as the team describes in their study published in the journal Science Signaling, they put the mice through two main tests. In the first, they had to remember if an object had been moved to a new spot, and in the second, they had to identify a new object compared to one they had seen before.

Their performance was measured by how much time they spent exploring. In tests in which objects were moved to new locations, female mice given acetate were much better at detecting the change. They spent more time investigating new spots, which suggests their brains had a much stronger memory of where the objects used to be. Male mice given acetate could perform these tasks, but they did not receive such a strong memory boost.

Molecular changes

To understand what was happening in the female brain, the team studied the dorsal hippocampus, a key region for memory. They discovered that acetate triggered a chemical change known as acetylation on a protein called H2A.Z.

This change to H2A.Z, a building block of the chromatin that makes up our chromosomes, caused the entire structure to physically loosen. When this happened, there was an increase in the activity of genes involved in learning. In female mice, this resulted in higher levels of memory-related genes, such as Nr4a3 and Ptgs2. In male mice, acetate did not increase H2A.Z acetylation. Their dorsal hippocampus chromatin did not open as much as in females.

If acetate causes a similar reaction in humans, the researchers believe it could open up a new type of therapy for women who are more likely to be affected by Alzheimer’s disease and age-related decline.

“Our findings suggest that acetate treatment could be a promising, noninvasive approach to enhance memory, particularly in females, who are disproportionately affected by both age-related cognitive decline and Alzheimer’s disease.”

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