Combination of Voluntary Wheel Running and Oral Intake of Lactate Improves Object and Spatial Recognition Memory in Association With Hippocampal Insulin-Like Growth Factor-1 in Mice.

Lactate is a food component that is sometimes also used as a food additive. Recent research has reported that lactate may be a crucial signaling molecule and energy substrate. Furthermore, lactate has been suggested to play a crucial role in learning and memory in the brain. It has been reported that high-intensity exercise improves cognitive function via an increase in the blood lactate concentration. However, most studies have focused on the intraperitoneal administration of lactate or on endogenous lactate elevation via high-intensity exercise, rather than on oral intake. Rather than exercise or lactate alone, the combination of the two might further enhance cognitive function. After confirming that 50 mM of lactate (L50) intake alone did not improve cognitive function, we demonstrated that the combination of voluntary exercise and L50 for 4 weeks significantly improved learning and memory in mice, despite the fact that exercise alone did not (p < 0.05). Mechanistically, this cognitive boost was associated with enhanced protein expression of synaptic plasticity markers, a significant increase in hippocampal neurogenesis, and a significant elevation in insulin-like growth factor-1 protein levels, along with activation of calcium calmodulin-dependent protein kinase II in the hippocampus. This effect was notably independent of changes in brain-derived neurotrophic factor expression levels. These results indicate that lactate might be beneficial as a dietary supplement during exercise that enhances learning and memory in both young and older people.