Running the stress away

Jul 10 2013 Published by under Behavioral Neuro

Whenever you get really stressed out, do you ever get the urge to Literally? Ok, maybe most of us run in the direction of the nearest bakery. But running (or otherwise doing long term exercise, probably not just a jog around the block) really can help with anxiety. But how does it work?



Schoenfeld et al. "Physical Exercise Prevents Stress-Induced Activation of Granule Neurons and Enhances Local Inhibitory Mechanisms in the Dentate Gyrus" Journal of Neuroscience, 2013.

In this study, the authors wanted to examine how exactly exercise can protect the brain from anxiety-inducing (the sciencey word here is anxiogenic, impress your friends!) effects of stress. But if you're going to be looking deep in the brain, you probably don't want to be taking human runners for this. Instead, they took mice, who, it turns out, like to run quite a bit. If you give a mouse access to a running wheel, he'll go to town on that thing for several hours of the day.

The scientists compared two sets of mice, those who had been giving running wheels for three weeks and those who hadn't, in their responses to stress. In this case, they used cold water swim stress. Mice swim very well, but they generally don't like it, especially if the water is cold. So after exposure to a swim in a bucket of cold water, normal mice will show signs of stress and anxiety, things like spending less time in the open arms of a maze (mice like the closed, confined and dark arms). They also will show "activation" of neurons in areas of the brain like the hippocampus. This usually mean expression of immediate early genes, genes which are activated very quickly in response to a signal, and which then serve as a signal for later responses. But how does it differ if you compare normally stressed mice with mice who were allowed to run first?

(Figure 1 E from the paper. Sadly it is small, and some of the behavioral data isn't included, because J Neuro eliminating supplemental data means people force ALL THE THINGS into the regular paper, rather than...maybe going with a slightly smaller "story", because reviewers refuse to change their demands. But more on that for another time)

What you can see above are measures of labeled cells in the hippocampus, that are screened for the immediate early genes c-fos and arc. You can see that in the sedentary mice (sed) these gene markers are increased after stress (dark bars), while in the running mice, they aren't significantly increased. It looks like running in mice protects them from these increases. The runner mice also showed less anxiety like behavior, spending more time in the open arms of an elevated maze (before stress, I would have liked to see after stress and how it measured up).

But WHY are the running mice protected from this?

What you can see above are levels of GABA, a neurotransmitter (chemical messenger) that is often associated with inhibiting the activity of other neurons (many current anti-anxiety drugs on the market, for example, increase GABA signaling). You can see above that mice who ran before stress (black squares) had higher levels of GABA during and immediately after stress than those who didn't. Higher levels of GABA in the hippocampus might be able to inhibit the neurons that would usually produce c-fos and arc in response to stress, and this might be what causes the runner mice to relax.

But how do you prove this? Well, you can block GABA receptors in the hippocampus, and see how the running mice then react.

What you can see above is sedentary mice (left), running mice (middle), and running mice given an injection of bicuculline into the ventral area of the hippocampus (where they previously found the biggest changes in c-fos and arc). Bicuculline inhibits GABA-A receptors, and so will help block the increased GABA signaling that is occurring in the running mice, to see the effect that it has. The test here is the elevated plus maze, a measure of anxiety like behaviors in mice. Normal mice spend less time in the open arms (the white bars), preferring the dark, closed off arms. The running mice, however, are pretty chill, and spend more time in the open arms of the maze (black bars). But if you block their GABA signaling with bicuculline (grey bars), their normal anxiety-like behavior is restored. This does a pretty good job of showing that it's the increased GABA signaling in running mice that helps protect them from the hippocampal signaling induced by stress, and the cellular changes that go along with it (though it would have been nice to see changes in arc and c-fos as well, but they've definitely got plenty of data for such a short paper).

So long term exercise (three weeks, in this case), really can help your anxiety and stress, by increasing GABA in the hippocampus (of mice, anyway). Do you need another excuse to get out and go? Me, I'm headed to the gym.

Schoenfeld et al. "Physical Exercise Prevents Stress-Induced Activation of Granule Neurons and Enhances Local Inhibitory Mechanisms in the Dentate Gyrus" Journal of Neuroscience, 2013. DOI.


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