Physical exercise activates a PVN-NAc oxytocin circuit to relieve stressinduced depressive-like behaviors

Physical exercise is known to reduce depression, but the underlying brain mechanisms SAMPLE ABSTRACT TEMPLATE  remain unclear. Based on a chronic restraint stress model in mice, we showed that 4-week treadmill exercise profoundly maintained normal neural activity in the nucleus accumbens (NAc), in association with the prevention of depressive-like behaviors. Microarray analysis conducted in the NAc revealed that the oxytocin (OT) receptor displayed the most significant differential expression, implying a crucial involvement of OT signaling in exercise-induced antidepressant effects. In vivo fiber photometry revealed disrupted OT release in the NAc and altered activity of OT neurons in the paraventricular nucleus (PVN) and their projections to the NAc in stressed mice, which were restored by exercise. Moreover, we found that stress-induced depressive-like behaviors were prevented by activation of PVN-NAc OT circuit. Additional inhibition of PVN-NAc OT circuit blocked the antidepressant effects of exercise in stressed mice. In summary, our findings reveal a novel role of PVN-NAc OT circuit in regulating depressive-like behaviors, which is required for the antidepressant effects of exercise. This novel neural circuit mechanism provides an explanation for brain network adaptations upon exercise and also suggests a promising therapeutic target for depression.

Weina Liu, the young scholar of ‘‘Changjiang Scholars Programme of China” rewarded by the Ministry of Education, the Vice Dean of College of Physical Education and Health, East China Normal University. She has published more than 60 academic papers, 25 papers were Indexed in SCIE and SSCI as the first/corresponding author (12 in top journal), 13 papers in Sports Science-the authoritative journal of sports science in China. She has presided over more than 10 projects, including the National Natural Science Foundation of China and the Key Program of National Social Science Fund of China, etc.