"These studies are focusing on the effects of exercise itself on chemicals known to protect and strengthen synapses," Rhodes explained. "But too much of it is not necessarily a good thing."

High runners tend to "max out" in the production of the BDNF and neurogenesis, Rhodes said. And that topping-out effect may be what prevents learning.

A high-running mouse's inability to learn as well as a normal mouse could be due to less biological reasons, Rhodes points out. "It is possible that they're so focused on running, they can't think of anything else," he said.

Rhodes and colleagues at the University of Wisconsin at Madison, the University of California at Riverside and The Salk Institute also emphasize that the functional significance of the exercise-induced increases in BDNF and neurogenesis is not known.

Rhodes suggests that when a high-running mouse exercises, stress is placed on its hippocampus and the development of new neurons becomes a protective response. No one has yet tested whether hyperactive wheel running exercise actually kills or damages neurons in the hippocampus, he said.

"The reason why these good things are happening is they may clean up some of the mess," he said. "Knowing that, you wouldn't expect high runners to get any benefit from it."

One thing is clear: Exercise greatly activates the hippocampus. Rhodes and his colleagues have conducted research that also shows the intensity of exercise is linearly related to the number of neurons that are activated in a subregion of the hippocampus called the dentate gyrus.

In addition, they have demonstrated that when mice are kept from their normal running routine, brain regions involved in craving for natural rewards such as food, sex and drugs of abuse become activated. It is allowing Rhode
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Contact: Jonathan Modie
modiej@ohsu.edu
503-494-8231
Oregon Health & Science University
26-Sep-2003