#Memory-boosting effects of working out could be bottled in ‘exercise pill’

Forget the red pill and blue pill, how about an “exercise pill”?

Exercise is integral to health — both of the body and the brain, especially as we age — and researchers at the University of California, San Francisco, are studying ways in which individuals could get the cognitive benefits associated with exercise in pill form.

Although there is evidence that working out can help keep neurological disease, including dementia and Alzheimer’s, at bay, regular exercise is a difficult habit to maintain as our metabolism slows and joints begin to creak.

“If there were a drug that produced the same brain benefits as exercise, everyone would be taking it,” said study senior author Saul Villeda, an assistant professor of anatomy. “Our study suggests that at least some of these benefits might one day be available in pill form.”

In a study of aging mice, researchers found that the rodents who clocked more activity had higher concentrations of the enzyme Gpld1 in their blood. Stemming from the liver, the protein’s prevalence also correlated with greater cognitive ability, according to their report, published July 10 in the journal Science.

In support of the study, data provided by the UCSF Memory and Aging Center also showed elevated levels of Gpld1 in elderly humans who can and do exercise regularly.

However, they also found that the learning and memory benefits associated with the enzyme when created through exercise were equal to those of the individual elder mice that received an artificial boost of Gpld1 through transfusion.

For one month, researchers in Villeda’s lab gave sedentary mice transfusions of blood coming from mice that had exercised consistently for seven weeks. The experiment prompted a significant intellectual improvement in the sedentary mice, comparable to their donors. A look at their brains revealed also a physical difference: the formation of new neurons in the hippocampus, the area of the brain associated with memory.

“To be honest, I didn’t expect to succeed in finding a single molecule that could account for so much of the benefits of exercise on the brain. It seemed more likely that exercise would exert many small, subtle effects that add up to a large benefit, but which would be hard to isolate,” Villeda said. “When I saw these data, I was completely floored.”

“This is a remarkable example of liver-to-brain communication that, to the best of our knowledge, no one knew existed,” he said. “It makes me wonder what else we have been missing in neuroscience by largely ignoring the dramatic effects other organs might have on the brain, and vice versa.”