Exercise effects that enhances hippocampus based cognitive function and the underlying molecular mechanisms

Although wheel running improves hippocampus-based cognition, with it optimum exercise intensity is not maintained. To resolve this, we developed an animal exercise model using a treadmill, where mild (<LT), moderate (@LT) and hard (>LT) intensity exercise is determined based on individual lactate thresholds (LT@50% VO_2max), and applied it in subsequent exercise neuroscience studies. We found that mild exercise (ME) activates neuronal c-fos accumulation in the dentate gyrus, CA1 and CA3. This was confirmed by a physiological study where ME led to hyperemia in the hippocampal CA1 via NMDA-NO signaling, leading us to postulate that ME enhances adult hippocampal neurogenesis (AHN) and spatial memory. Indeed, we found that two weeks of chronic ME training promoted AHN, and that a further six weeks of chronic ME training led to enhanced AHN and spatial memory. Neuronal substrates behind the beneficial effects are still being debated, although neurogenic androgen, together with IGF-I, is known to be involved in the development of AHN, which may result in improved memory. The latest DNA microarray analysis implies that lipid metabolism, protein synthesis and inflammatory response are associated with ME-enhanced AHN. This provides new insight into ME benefits, which is necessary for translational studies from animals to humans.