Regular exercise reduces the risk of cardiovascular diseases, stroke, hypertension, and diabetes and enhances bone, muscle, and mental health. Recent evidence strongly suggests that aerobic exercise promotes adult neurogenesis in the hippocampus, improving synaptic plasticity. This study aimed to identify target miRNA candidates regulated by aerobic exercise that may contribute to enhanced hippocampal neurogenesis.

Male and female C57BL/6 mice (13 weeks old) were divided into two groups: a control group housed in locked-wheel cages and an exercise group housed in wheel-equipped cages for two weeks. The mice in the exercise group had free access to the running wheel in each cage, while the control mice were unable to use the wheel, as it was secured with a cable tie. Each group consisted of four mice. Total RNA was extracted from the dissected mouse hippocampi and used for RNA sequencing. Differentially expressed miRNAs were then identified based on gender and/or the exercise conditions.

A total of 698 miRNAs were identified as differentially expressed across the groups. A two-way ANOVA revealed that 67 miRNAs were differentially expressed by sex and 87 miRNAs by exercise (p < 0.05). Additionally, 55 miRNAs were influenced by both factors. The expression levels of miR-7b-3p, miR-212-3p, and miR-132-3p were significantly increased by exercise in both the male and female groups, while miR-12200-5p expression was reduced by exercise (p = 0.0135) but was lower in the male group overall.

This study shows that aerobic exercise alters the expression of specific miRNAs in the hippocampus, with some differences between males and females. miR-7b-3p, miR-212-3p, and miR-132-3p were significantly increased by exercise in both sexes, while miR-122000-5p was reduced. These miRNAs may play important roles in exercise-induced neurogenesis and brain health. Future research will focus on examining the effects of these target miRNAs on hippocampal neurogenesis.