A number of studies have suggested exercise can boost cognitive function, but the underlying mechanisms of this association have been unclear. Now, new research sheds light on how running can improve learning and memory.

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Researchers suggest running increases levels of a protein that boosts memory recall.

In a mouse study published in the journal Cell Metabolism, investigators found running increased levels of a protein called cathepsin B, which spurred brain cell growth, improving the memory recall of mice following a location task.

Encoded by the CTSB gene, cathepsin B is perhaps most well known for its role in cancer progression; the protein is secreted by tumors and is believed to fuel cancer metastasis.

Other studies have suggested cathepsin B plays a role in the clearance of beta-amyloid plaques, which are known to contribute to the development of Alzheimer's disease and other neurodegenerative disorders.

Senior author of this latest research, Henriette van Praag, a neuroscientist at the National Institute on Aging (NIA) - part of the National Institutes of Health (NIH) - and colleagues say their study is the first to link cathepsin B with spatial learning.

Cathepsin B levels increased in response to exercise

The researchers decided to focus on the role of cathepsin B in response to exercise after screening a number of proteins likely to be secreted by muscle tissue and transported to the brain.

In a lab dish, the team exposed muscle cells to various exercise-mimicking compounds and found that cathepsin B was the most secreted protein.

The researchers also identified high levels of cathepsin B in the blood and muscle cells of mice that had been running on an exercise wheel every day for several weeks.

What is more, on applying the protein to brain cells, the team found that it triggered the production of molecules that play a role in brain cell development and growth - a process known as neurogenesis.

With these findings in mind, van Praag and colleagues set out to investigate how cathepsin B might impact memory recall in response to physical activity.

Memory boosted by cathepsin B after running

To reach their findings, the team used two groups of mice: one group was unable to produce cathepsin B in response to both exercise and sedentary behavior, while the other group had normal production of the protein.

Every day for 1 week, both groups of mice engaged in a Morris water maze test, which required them to identify the location of a platform within a small pool.

The researchers explain that normal mice usually learn the location of a platform after a few days of learning the circuit.

However, when both groups of mice ran before the water maze test, the researchers found that the mice lacking the ability to produce cathepsin B could not recall the location of the platform, but the normal mice could.

The team believes these findings indicate that cathepsin B may play an important role in memory in response to exercise.

"Nobody has shown before cathepsin B's effect on spatial learning. We also have converging evidence from our study that cathepsin B is upregulated in blood by exercise for three species - mice, Rhesus monkeys, and humans.

Moreover, in humans who exercise consistently for 4 months, better performance on complex recall tasks, such as drawing from memory, is correlated with increased cathepsin B levels."

Henriette van Praag

Based on this latest study and previous research linking cathepsin B levels to various diseases - such as cancer - the researchers speculate that different levels of the protein and different physiological conditions pose different outcomes.

The team now plans to gain a better understanding of how cathepsin B crosses the blood-brain barrier, as well as how the protein triggers neurogenesis to improve memory.

In the meantime, van Praag says the current findings highlight the importance of a healthy lifestyle.

"People often ask us, how long do you have to exercise, how many hours?" she adds. "The study supports that the more substantial changes occur with the maintenance of a long-term exercise regimen."

Learn how exercising 4 hours after learning can boost memory.