Running for New Neurons

Two decades of research show that running, brisk walking, swimming or cycling all help protect your memory as you age. But a new study by Henriette van Praag, Ph.D., associate professor in the Charles E. Schmidt College of Medicine, pinpoints that consistent exercise modifies and maintains connections in your brain.

The hippocampus is a part of the brain that is essential for forming new memories and learning. Throughout a rodent’s life, new nerve cells, called neurons, are added to this region, van Praag said, and that voluntary wheel running increases the number of new neurons. However, it is unclear whether the wiring of new neurons born in young adult mouse brains and their connections in the brain’s network change with age. The results of her new study, published in the journal eNeuro, reveal that if mice exercise into midlife, the neurons generated as an adult survive in larger numbers and are connected in a manner that benefits memory.

“If you have any kind of electrical circuit, over time the wires can become frayed or you can lose the plugs,” van Praag said. “We wanted to see if the exercise played any role in either maintaining that circuit or modifying it in some way that might be important for memory.” In other words, this study was aimed at seeing if exercise changes the connections that these newly born neurons make, she said.

To study the long-term effects of running, van Praag and her team had a two-step process to examine the neurons generated in young adult mice, which are about 2 months old at the onset, once they hit middle-age to create a map of the neurons and their connections.

First, they injected a type of virus to tag stem cells in the hippocampus that would become neurons over the course of several weeks, and made the cells express a unique receptor, like a docking point, she said. Then, six months later when the mice were middle age, they injected a rabies virus engineered to selectively trace, or link up to, that docking point of the tagged neurons. “It’s like a lock and key system,” van Praag said.

With this tagging system of the neurons, the researchers could then quantify the neurons, their number of connections in the brain and where they were located. “We basically made a map of the network and show how it is modified by running.” van Praag and her co-authors found that in mouse models, exercise benefits areas in the hippocampus region of the brain that acquire new memories. However, van Praag said, the team also found that adjacent regions of the brain, called the periand entorhinal cortical region increased innervation of new neurons, which is “important for our ability to find our way in the world — to navigate. Also, in particular, it’s important for us to remember the context or the circumstances of an event,” she said. Running promoted the survival of adult-born neurons, but also helped them maintain their connections in these areas.

But can running get our brains to the finish line? van Praag’s research is also exploring “how these circuits are maintained and formed over the lifespan, what happens if you stop running in midlife or before midlife, and how long are these network modifications maintained into old age?”