Longevity Briefs: Just A Few Days Of Junk Food Impacts Memory In Mice

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

We all know that high fat diets are bad, contributing to weight gain and increasing your risk of multiple age related diseases, including heart disease and even neurodegenerative disease. But it’s OK to binge on fatty foods occasionally while maintaining a healthy weight, right? Unfortunately, that might be wishful thinking. In this study, researchers feed mice a high-fat diet for just a few days and observe a significant health impact.

The discovery:

Researchers took adult mice and fed them either a normal diet or a high-fat diet: 58% fat, 25% carbohydrates, and 17% protein. This is a similar nutrient distribution to a typical fatty western diet. After two days, researchers observed that the body weight and blood sugar levels in the high-fat diet mice was not significantly altered due to the short duration of the experiment. These mice also appeared to be more physically active. Despite this, the high-fat diet was associated with significantly worse performance in cognitive tests involving spatial memory when compared to the control mice.

How could just a few days on a high fat diet have impacted spatial memory? The researchers focused in on a specific region of the hippocampus called the dentate gyrus, which plays an important role in the recognition of novel spaces. They observed that mice on the high-fat diet showed increased activity of a subset of neurons in the dentate gyrus called cholecystokinin-expressing interneurons (CCK-INs). These neurons inhibit other neurons within the hippocampus and are glucose-inhibited. That means that when glucose (sugar) is low, CCK-INs become more active and inhibit nearby neurons.

Previous research had indicated that high fat diets resulted in reduced activity of GLUT1, the main transport protein that carries glucose from the blood and into the brain. It is therefore possible that the high fat diet reduced the supply of glucose to CCK-INs, which already sit further away from the blood supply compared to other hippocampal neurons, thereby increasing their activity and dampening that of nearby neurons. In support of this hypothesis, the researchers found that when they genetically blocked an enzyme (called PKM2) that breaks down glucose, thereby raising glucose levels in CCK-INs, the mice consuming the high-fat diet performed better in spatial memory tests.

Finally, researchers looked at spatial memory in mice that had been fed a high-fat diet for 10 weeks, resulting in them becoming obese. They found that these mice had spatial memory deficits, but genetically blocking PKM2 prevented this effect, suggesting that the short and long-term impacts of the high-fat diet on memory shared a common mechanism.

The implications:

It’s quite surprising that such a brief exposure to a high-fat diet was able to have an effect on memory. It appears that cells in the brain respond very quickly to changes in nutrition, with immediate consequences for cognitive function. The good news is that this might work both ways, with healthy dietary changes or practices like fasting having an immediate positive impact on cognition. Another pressing question is whether brief and infrequent lapses into a high-fat diet build up over time to a more long term impact on cognitive function.