As people age, they often can't quite remember where they put things they always use. Getting lost also becomes more common. A path has opened to develop a drug that can boost memory for spaces and places. Animal studies found that a byproduct produced when the body breaks down alcohol, glucose, or high-fiber foods may improve memory.
A research team led by Gabor Egervari, a professor at the University of Washington School of Medicine, said on the 24th (local time) in the journal Science Signaling that "injecting acetate (CH₃COOH-) into mice improved the function of the dorsal hippocampus, the brain's center for place memory."
Acetate is a substance in which one hydrogen has been removed from acetic acid (CH₃COOH; vinegar), leaving it in an anionic state. However, acetate was effective only in females in animal experiments. If the same holds true in humans, it is expected to help maintain cognitive function in older women.
◇ Remembered the relocated object and explored more
The hippocampus is the brain's center for memory and learning, and the dorsal part mainly handles place memory. It is essential for remembering and finding a favorite restaurant. Unlike the ventral hippocampus, which deals with emotions and stress, the dorsal part focuses relatively more on cognitive functions.
The researchers gave mice two identical objects and let them explore for 10 minutes. After 24 hours, they showed the objects again. One had been moved to a different location. Egervari said, "Mice with intact memory remembered that the object had been in a different location yesterday."
Mice with better memory played more with the object whose location had changed. The change in location provided a new stimulus. It was different for mice with impaired memory. They played with the two objects for the same amount of time. This can be explained by their failure to recognize the change in location and seeing them as identical objects.
Next, one group of mice received acetate while the other group received a placebo of saline. In the same memory test, female mice given acetate performed better than those given saline. Male mice did not show improved memory even when given acetate.
This experiment used sodium acetate (CH₃COONa). Because injecting acetic acid itself can damage tissues, the team tested a neutral substance in which sodium, instead of hydrogen, is bound. When sodium acetate is dissolved in saline, it dissociates into sodium and produces acetate.
Acetate is a human metabolic byproduct, but it is also widely used in the food industry in compound forms bound to ethyl or butyl groups. It is mainly used to impart fruit flavors to gum, candy, bread, and ice cream, or to decaffeinate tea and coffee.
◇ Same genes, different structure, better effect
The researchers said acetate enhanced memory by changing structure while leaving genes themselves intact. In the brain, acetate altered gene expression through histone acetylation. Just as thread is wound around a spool, DNA strands containing genes are wrapped around proteins called histones. For a gene to operate, acetyl groups must attach to histones so the DNA strand unwinds.
The team confirmed histone acetylation on the H2A.Z protein, which is associated with long-term memory. Then the activity of learning-related genes increased. In female mice, expression of memory-related genes such as Nr4a3 and Ptgs2 increased in the dorsal hippocampus. This is precisely what is called an epigenetic effect. As the name suggests, the DNA genetic information inherited at birth remains unchanged, but later structural changes in DNA alter gene function.
Razia Zakarya, an epigenetics researcher at the University of Technology Sydney, told Nature, "This study shows how a byproduct of digestion forms memories through epigenetic mechanisms," and noted, "Acetate is effective only when neural activity occurs during learning." In other words, it changes gene structure only when the brain is forming a memory.
The researchers said that if acetate has the same effect in humans, it could open the way to developing treatments for women, who are more vulnerable to cognitive decline related to Alzheimer's disease or aging. The team said it plans to study whether acetate injections can prevent memory loss in mice with cognitive impairment.
References
Science Signaling (2026), DOI: https://doi.org/10.1126/scisignal.aec0496