Compounds that increase muscle endurance also enhance cognition

Recent experiments from Kobilo et al. build on several studies that have shown that exercise enhances cognition (in both humans and mice). They show that giving sedentary mice either of two drugs that induce the same kinds of changes in their muscles that exercise does enhances their performance in subsequent tests of memory and learning. Since these drugs do not cross the blood-brain barrier, peripheral triggers appear be activating the cellular and molecular cascades in the brain that lead to improvements in cognition.

Physical activity improves learning and hippocampal neurogenesis. It is unknown whether compounds that increase endurance in muscle also enhance cognition. We investigated the effects of endurance factors, peroxisome proliferator-activated receptor δ agonist GW501516 and AICAR, activator of AMP-activated protein kinase on memory and neurogenesis. Mice were injected with GW for 7 d or AICAR for 7 or 14 d. Two weeks thereafter mice were tested in the Morris water maze. AICAR (7 d) and GW improved spatial memory. Moreover, AICAR significantly, and GW modestly, elevated dentate gyrus neurogenesis. Thus, pharmacological activation of skeletal muscle may mediate cognitive effects.