The protein cathepsin B can be directly traced from the muscles to the brain in mice, researchers said. Also, after a run, protein levels increased in blood in mice, monkeys, and humans.
"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," said Henriette van Praag, a neuroscientist at the National Institute on Ageing in the US.
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 neurogenesis.
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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.
After doing this task for a few days, normal mice eventually learn where to find the platform.
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.
"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," he said.
"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," said van Praag.
This previously unrecognised function of cathepsin B may be controversial. The protein is known to be secreted by tumours and has been implicated in cell death and amyloid plaque formation in the brain.
Researchers hypothesise that different levels of the protein and different physiological conditions may yield different effects.
The study was published in the journal Cell Metabolism.