Leptin in hippocampus mediates benefits of mild exercise by an antioxidant on neurogenesis and memory

Significance Leptin (LEP), produced and acting in the hippocampus, mediates enhancement by mild exercise (ME) of hippocampus-related memory and neurogenesis, which are further increased by an antioxidant carotenoid, astaxanthin (AX). Both are facilitated by the administration of ME or AX alone. The up-regulation of the LEP gene and LEP protein expression in the hippocampus by ME is further elevated when combined with AX. Consistently, the combined interventions increased hippocampal LEP protein. In LEP-deficient ob/ob mice, LEP replacement in the brain restored the ability of ME+AX to enhance hippocampal function. Thus, a combined lifestyle intervention based on ME, including yoga and tai chi, and specific dietary supplements that include antioxidants may together improve cognition and possibly retard cognitive decline in humans.