Exercise-Induced Hippocampal Neurogenesis Is Attenuated by Inhibition of Monocarboxylate Transporter 2

Several studies have suggested that lactate mediates exercise-induced hippocampal neurogenesis. To investigate this, we used a monocarboxylate transporter (MCT) inhibitor, alpha-cyano-4-hydroxycinnamic acid (4CIN), to attenuate the signaling effect of endogenous lactate in the hippocampus. Ten-week-old ICR mice were intraperitoneally injected with 100 mg/kg 4CIN before beginning moderate-intensity treadmill exercise 5 days a week for 8 weeks. After 8 weeks of intervention, we evaluated hippocampal neurogenesis, hippocampal protein expression relevant to neurogenesis, and learning and memory function using histology, western blotting, and behavioral tests, respectively. We found that the inhibition of MCT2 by 4CIN led to a reduction in the number of exercise-induced newly generated neurons in the dentate gyrus, and the hippocampal protein expression level of the neurogenesis marker was in line with these histological results. Furthermore, we showed that the inhibition of MCT2 negated the improvements in learning and memory induced by exercise training. Based on these results, we propose that lactate is a potential mediator of exercise-induced hippocampal neurogenesis.