In this study, we showed that the BDNF-FoxO1 axis in the mPFC is important for regulating depression-related behavior in postpartum female mice. We found that CUS can induce depression-related behavior in postpartum female mice and that a Bdnf-specific exon mRNA expression was decreased in the mPFC of female mice with depression-like behavior, resulting in low expression of total Bdnf mRNA that coincided with depression-related behaviors. The important finding was that postpartum female mice showed higher susceptibility to SCUS-induced depression-related behavior and that mPFC-specific BDNF-knockout induced differential behavioral phenotypes in virgin and postpartum female mice. Reduced FoxO1 levels in the mPFC were also involved in depression-related behaviors of CUS-treated postpartum female mice. Furthermore, mPFC-specific BDNF knockout also resulted in decreased modulation of FoxO1 in the mPFC. Collectively, these data provide strong evidence for the neuronal role of BDNF in PPD.
