A number of studies, principally involving rodents, have established that physical exercise stimulates the creation of new brain cells in the hippocampus. A recent study attempted to uncover more about the mechanism.
Using two drugs that work directly on muscles, producing the physical effects of exercise, the researchers compared the effects on the brain. One drug (Aicar) improves the fitness of even sedentary animals. The other drug increases the effects of exercise on animals that exercise, but has little effect on sedentary animals.
After a week of receiving one of the drugs, sedentary mice performed better on tests of memory and learning, and showed more new brain cells. These effects were significantly greater for those taking Aicar.
Because the drugs have very little ability to cross into the brain, this demonstrates that the neurogenesis results from exercise-type reactions in the muscles, not to brain responses to the drugs. Indeed, previous research has found that direct infusion of Aicar into the brain impaired learning and memory.
Aicar increases the muscles’ output of AMPK, an enzyme that affects cellular energy and metabolism. It’s speculated that some of this enzyme may enter the bloodstream and travel to the brain. Interestingly, as with neurogenesis, AMPK activity in muscles appears to decline with age. It may be that AMPK production could serve as a biomarker for neurogenesis, as well as being a target for improving neurogenesis.
These findings add weight to evidence for the value of aerobic exercise over other types of exercise (given that the mice exercise by running). However, I see that human research has found that resistance training (which is difficult to study in mice!) also increases AMPK activity.
Do note — if you are hopeful that drugs will relieve you of the need to exercise — that the benefits were not only smaller than those achieved from exercise, but also didn’t last. In those mice taking Aicar for a second week, their brains not only stopped deriving any benefit, but actually deteriorated.
 . Endurance factors improve hippocampal neurogenesis and spatial memory in mice. Learning & Memory. 2011 ;18(2):103 - 107.
Full text available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032576/