This exercise protein boosts your memory?

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After exercising in a running wheel, month-old neurons (green) are seen in the hippocampus of an adult mouse.
Credit: Henriette van Praag and Linda Kitabayashi

Exercise isn’t just great for your body – it’s fantastic for your mind too. People who exercise regularly tend to have more cells in the memory part of their brain – with a better memory to boot  but exactly how long runs in the park translate to cell growth is a little murky.

In Cell Metabolism today, neuroscientists in the US and Germany claim to have found a link between the protein cathepsin B, which is secreted by muscles into the bloodstream during exercise, and better memory in mice, monkeys and humans.

The adult brain is not a static organ. It undergoes new cell growth, called neurogenesis, via dividing stem cells that morph into neurons and wiggle around the brain.

This capacity for neurogenesis was discovered by neuroscientist Perry Bartlett, then at the Walter and Eliza Hall Institute in Melbourne, Australia, and colleagues in 1992.

In 2001, they isolated human brain stem cells for the first time, and found a population of stem cells residing in the hippocampus, a structure that consolidates memory and learning.

In the years since, scientists have found that exercise seems to boost neurogenesis  and more neurogenesis, the better an animal’s memory. 

But how exactly are exercise and cell growth linked? Do exercising muscles ooze a particular molecule that travels via blood to the brain to give neurogenesis a boost?

Hyo Youl Moon at the National Institute of Ageing in Baltimore, US, and colleagues started their search for such a molecule by scanning a range of proteins secreted by exercising muscle. An interesting candidate turned out to be cathepsin B.

Cathepsin B is an enzyme that breaks down other proteins. Its function seems contradictory to neurogenesis – it’s been linked to cell death.

But Moon and colleagues found mice that enjoyed a daily run on a running wheel ended up with higher levels of cathepsin B in their bloodstream and could learn faster than their sedentary counterparts.

Mice genetically engineered to be unable to produce cathepsin B, on the other hand, didn’t benefit from the daily runs. Their memory capacity didn’t differ from genetically engineered, but sedentary, mice.

And human and monkey participants, after four months of treadmill training, had higher cathepsin B blood levels and better memories than full-time couch potatoes.

When the researchers added cathepsin B to brain cells in a dish, the cells started producing neurotrophins – molecules that kickstart and nurse new cell growth.

This may seem like a cut-and-dried link between cathepsin B and neurogenesis. But mice genetically engineered to lack cathepsin B their whole life may end up with other, as-yet unknown effects.

Bartlett, now director of the Queensland Brain Institute at the University of Queensland, Australia, says the work is a “very neat”. But, he adds, “ideally, you’d turn off cathepsin B only in the hippocampus and only as an adult” to isolate its effects in the brain at the right time.

Indeed, the authors admit they don’t know how cathepsin B might penetrate the blood-brain barrier – a tightly packed layer of cells that line blood vessels and only selectively let molecules through – or how the protein behaves in different species.

Production of cathepsin B may even change with age.

But the take-home message, paper co-author Henriette van Praag says, is a consistently healthy lifestyle is the best way to beef up your brain: “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.”

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