Study helps explain why running improves memory

WASHINGTON - Here's another reason for starting running: It may help improve your memory by releasing a protein that can be directly traced from the muscles to the brain in mouse experiments.

After a run, levels of the protein, called cathepsin B, increased in the blood of mice, monkeys, and humans, according to the study published this week in the U.S. journal Cell Metabolism.

"We wanted to cast a wide net," said senior author Henriette van Praag, a neuroscientist at the U.S. National Institute on Aging.

"Rather than focus on a known factor, we did a screen for proteins that could be secreted by muscle tissue and transported to the brain, and among the most interesting candidates was cathepsin B."

In the study, researchers first exposed muscle cells in a dish to compounds that mimic exercise and observed that the presence of cathepsin B production noticeably increased in the conditioned media of the cultures.

High levels of the protein were also found in the blood and muscle cells of mice that spent time daily for several weeks on their exercise wheels.

Additionally, when cathepsin B was applied to brain cells, it spurred the production of molecules related to the generation of new brain cells.

The researchers then compared memory recall in normal mice with that in mice lacking the ability to produce cathepsin B under both sedentary and running conditions.

Over the course of a week, both sets of mice were given a daily swim test in a water maze, which required them to swim to a platform hidden just below the water surface within a small pool.

The researchers explained mice usually learn where to find the platform after doing this for a few days.

However, when both groups ran before their daily swim test, the normal mice were better able to recall the location of the platform, while the mice unable to make cathepsin B could not remember its location, suggesting the potential of the protein in 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," said van Praag, who collaborated on the study with German researchers.

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

This previously unrecognized function of cathepsin B may be controversial, the researcher said.

The protein is known to be secreted by tumors and has been implicated in cell death and amyloid plaque formation in the brain. Other studies have found that cathepsin B is neuroprotective and can clear amyloid plaques.

Van Praag hypothesized that it could be different levels of the protein and different physiological conditions that yield different effects.

The researchers will next explore how cathepsin B is crossing the blood-brain barrier, how it is activating neuronal signalling, growth, and connections, whether it behaves the same in different species, and how production of the protein changes with age.

"Overall, the message is that a consistently healthy lifestyle pays off," van Praag said. "People often ask us, how long do you have to exercise, how many hours? The study supports that the more substantial changes occur with the maintenance of a long-term exercise regimen."