For a while now, researchers have known that aerobic exercise improves memory and learning. However, no one really knew how until now.

In the journal Cell Metabolism, scientists reported that a protein called cathepsin B, a substance produced and released in the muscles, is necessary for improving exercise-induced memory and brain cell production in mice. The researchers also demonstrated that the protein has a positive effect on monkeys and humans.

“This is a long chain of events, from exercise to muscle to brain to cognition,” said Paul Frankland, a neuroscientist at the University of Toronto, “but the authors do a great job at demonstrating each of the links.”

The findings came after after Henriette van Praag, an investigator of brain science at the National Institute of Aging, and colleagues decided to do a screen for proteins that were secreted by muscle tissue and then traveled to the brain. The search revealed cathepsin B as one of the most interesting candidates.

Experiments showed that cathepsin B levels increased in the blood and muscle tissue of mice that exercised for two to four weeks. Moreover, with the rise in protein levels, the mice performed better on a memory test requiring them to swim to a platform hidden under a small pool.

Also in mice, the team found that the protein was spurring the production of new cells and connections in the hippocampus, a portion of the brain that is fundamental to memory.

The team wanted to assess how the substance affected other species, so they looked at rhesus monkeys. After exercising, the animals showed an upregulation in cathepsin B.

Next, the researchers studied 43 university students that were couch potatoes. Half of the students remained inactive. The other half underwent four months of treadmill training.

Not surprisingly, the active students showed an increase in their cathepsin B levels as their fitness improved. Not to mention, they did better on a memory task: reproducing a geometric design they’d seen a few minutes earlier.

Cathepsin B could be one of many factors linking exercise and brain function, points out van Praag.

Much more research needs to be performed on the protein, especially after previous research has linked it to neuronal cell death following brain injury and brain plaques associated with Alzheimer’s disease.

Consequently, van Praag is trying to keep her own cathepsin levels up naturally by jogging, rather than running on a treadmill.