The potential contribution of light-intensity exercise-induced miR-486a-3p secretion on enhancing empathic behavior in mice: Possible involvement of brown adipose tissue

Empathy plays a crucial role in the maintenance of interpersonal relationships among mammals. Remarkably, engaging in light-intensity exercise has been identified as a facilitator of empathic behavior, a phenomenon associated with the upregulation of miR-486a-3p in the insular cortex. However, it remains to cover the contribution of miR-486a-3p and the mechanisms of changing levels of that in the insular cortex with light-intensity exercise. We initially assessed the impact of light-intensity exercise (7.0 m/min, 30 min/day, five days/week for four weeks) on helping behavior, mRNA in their insular cortex, and the secretion of exosomal miR-486a-3p from their peripheral tissues. Subsequently, we explored the effects of a daily intraperitoneal injection of miR-486a-3p mimic over a two-week period on helping behavior. The intervention of light-intensity exercise, which enhanced helping behavior, resulted in elevated levels of miR-486a-3p in the insular cortex and exosomal miR-486a-3p in the plasma. Interestingly, the exercise intervention led to a marked increase in exosomal miR-486a-3p derived from brown adipose tissue, whereas no such increase was observed in exosomes originating from the gastrocnemius muscle or the liver. Moreover, the administration of mmu-miR-486a-3p mimic exhibited a similar enhancement of helping behavior in mice. Notably, both the exercise intervention and miR-486a-3p mimic treatment led to the downregulation of Pten mRNA and upregulation of Bdnf mRNA in the insular cortex. Our findings suggest that the increase in peripheral-derived miR-486a-3p, originating from the brown adipose tissue, may support empathy enhancement associated with light-intensity exercise. Additionally, miR-486a-3p may have similar effects to light-intensity exercise in relation to empathy, providing a potential approach for addressing empathy-related behaviors.