Four weeks of light-intensity exercise enhances empathic behavior in mice: The possible involvement of BDNF

Empathy is one of the essential functions of mammals for maintaining relationships with others. Physical activity contributes to enhancing empathic attitude and behavior; however, it is remained to cover the effective intensity of exercise on mammal empathy. Here, we tested the effects of light-intensity exercise, which has beneficial effects on expressing neurotrophic factors in the brain, on empathic behavior. Eight-week-old male C57BL/6 mice were subjected to forced wheel running at light-intensity (7.0 m/min, 30 min/day, 5 days/week) for 4 weeks. Then, all mice were subjected to helping behavior to evaluate their empathic behavior. The insular cortex was collected for analyzing the expressions of mRNA and miRNA. Four weeks of light-intensity exercise enhanced helping behavior. Exercised mice exhibited higher Bdnf gene expressions in the insular cortex than sedentary mice. In addition, there was a significant positive correlation between mRNA levels of Fndc5 and Bdnf in the insular cortex. Based on miRNA sequencing, 26 out of 51 miRNAs were significantly upregulated, and 25 out of 51 miRNAs were significantly downregulated in the insular cortex of mice with exercise. There were significant correlations between 11 out of 51 miRNAs and helping behavior; miR-486a-3p, which relates to FNDC5 expression, was contained. These results imply that miR-486a-3p/Fndc5/Bdnf pathway in the insular cortex would be a possible target for treating empathy.