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There exists a large and soothing body of scientific literature suggesting that regular exercise can improve someone’s mood and fight anxiety. And then there is this experiment from Germany, in which researchers placed running wheels in the cages of a group of laboratory mice and let them exercise at will.

Mice generally love to run, and these rodents spent almost every waking hour on their wheels, skittering through more miles than most animals are allowed to complete during exercise studies, averaging about seven miles per mouse per day. The scientists, from the Central Institute of Mental Health Mannheim, then placed these avid runners in unfamiliar situations. What they found was surprising, in part because it contradicted earlier experiments by other researchers. The mice froze or quickly fled to dark corners, behaviors considered by some researchers to signify anxiety. It was as if the marathon runners in this experiment had become more anxious and neurotic than the nonrunners, presumably because of the volume of their running.

The apparent implication of that finding — that too much running makes an animal a nervous wreck — might seem disconcerting. But as this study, published in the journal Hippocampus, and additional new research makes clear, a great deal still needs to be understood about just how exercise affects mood.

To date, most research into the interplay of exercise and anxiety has focused on the actions of various neurotransmitters or chemical messengers within the brain, like serotonin and dopamine. But the German researchers weren’t looking at neurotransmitters. Their interest was in a different brain mechanism. They were trying to determine whether the formation of new brain cells, a process called neurogenesis, was making their lab animals nervous

Exercise spurs neurogenesis, a finding confirmed by seminal research completed a few years ago. This neurogenesis would seem to be completely laudable, since it occurs mostly in the hippocampus, a portion of the brain associated with memory and thinking. Rodents that have exercised and that have brains fizzing with new neurons tend to score well on tests of memory and cognition.

But the effects of neurogenesis on mood are murkier. A number of neurological case studies have reported that people and animals with lesions in the hippocampus — meaning fewer brain cells in that region — are less prone to anxiety than other people.

So could high volumes of running and the commensurately large amounts of neurogenesis in the hippocampus produce anxiety? The German work seemed to say yes, particularly a follow-up experiment by the same scientists published in September in the online journal PLoS One. In that study, the researchers radiated the brains of mice to prevent neurogenesis, and then let them run. The treated mice eagerly took to their wheels, but grew almost no new neurons. Afterward, placed in stressful situations, they remained calm, reacting much like sedentary mice.

It seemed that neurogenesis had been the culprit behind the earlier runners’ excessive anxiety.

But the scientists are quick to point out that these findings do not mean that human marathon and ultramarathon runners are necessarily at risk of developing mood problems. The “exercise schedule of mice is not comparable to human fitness training,” wrote Dr. Johannes Fuss and Dr. Peter Gass, the primary authors of the two studies, in a shared e-mail response to questions. With very rare exceptions, humans will not spend their entire waking hours running.

More important, it’s not clear whether the behavior of the nervous mice was necessarily anxiety as we might experience it. The exercised mice did frequently freeze and hide, but they are prey animals, a situation that does not reward insouciance. To be less anxious, if you are a mouse, Dr. Fuss and Dr. Gass wrote, “might not always be the best survival strategy.”

The German scientists, in focusing narrowly on neurogenesis, may also have underestimated the intricate and broad ways in which exercise affects the brain’s mood centers. A fascinating series of experiments conducted at Princeton University and presented at the 2010 annual meeting of the Society for Neuroscience in November showed that neurons born from running actually behave differently from other neurons. They are not as physiologically excitable, even in stressful situations. The Princeton scientists showed that after a rodent stress test, the hippocampi of running mice contained fewer proteins associated with neuron activity than the brains of sedentary mice, even though the runners had more neurons over all. The runners’ brain cells had remained, it seemed, more calm in the face of stress. Similarly, the scientists found, areas of the brain that would normally shoot stimulating messages to the hippocampus during and after stress were quieter in exercised mice.

“Thus,” the Princeton researchers concluded, “running may reduce anxiety-like behavior” despite increasing the number of new brain cells. Exercise had recalibrated the animals’ brains so that they were more serene.

What this emerging science means for those of us who regularly exercise is, admittedly, still being teased out by researchers. But other recent studies are encouraging. A review article published last year in The Archives of Internal Medicine, for instance, concluded that compared with sloth, “exercise training significantly reduced anxiety symptoms” in a group of people at risk for mood problems. And in a beguiling experiment also presented at the 2010 Society for Neuroscience meeting, scientists from the University of Oklahoma found that female rats allowed to run at a moderate pace for 10 to 60 minutes several times a week — my exercise regimen, in fact — behaved with robust mental health in stress tests. So whether you run on two legs or four, the message may be: relax.


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