Exogenous lactate augments exercise-induced improvement in memory but not in hippocampal neurogenesis

Adult hippocampal neurogenesis (AHN), the lifelong process of formation of new neurons in the mammalian brain, plays an important role in learning and memory. Exercise is an effective enhancer of AHN; however, the molecular mediators of exercise-induced AHN are unknown. Recently, lactate was considered as an important mediator of exercise-induced AHN. Therefore, we hypothesized that exercise with lactate intake could augment exercise-induced AHN. This study was conducted for 5 weeks with 7-week-old ICR male mice that performed mild-intensity exercise (just below lactate threshold, 55-60%VO_2max) with or without oral administration of lactate 5 days/week. Cell proliferation, neuronal differentiation, neurogenesis-relevant factors, reference and retention memory, and spatial working memory were evaluated at the end of the experiment. The results showed that AHN was enhanced by lactate intake, but exercise-induced AHN was not augmented by exercise with lactate intake. Nevertheless, exercise-induced improvement in reference and retention memory was augmented by exercise with lactate intake. And spatial working memory was promoted by the co-treatment, also protein expression of hippocampal FNDC5, BDNF, PGC1α, and MCT2 were elevated by the co-treatment. Therefore, our findings suggest that lactate has a potential to be developed as a novel supplement that improves the positive effects of exercise on the hippocampus and its cognitive function.