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Chunk #20 — Discussion

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The BDNF-FoxO1 Axis in the medial prefrontal cortex modulates depressive-like behaviors induced by chronic unpredictable stress in postpartum female mice.
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The incidence of depression is 2–3-fold higher in women than in men [40]. In particular the postpartum period is considered the time of greatest risk for women to develop MDD [41]. In order to address response of susceptibility in postpartum female mice, we applied a short term SCUS (3 days CUS), which is the usually used strategy to evaluate the susceptibility to stress [42, 43]. Our findings demonstrated that female mice after parturition showed similar depression-like phenotypes to virgin females, which means the parturition stress alone cannot induce depression, while postpartum female mice showed enhanced susceptibility to SCUS induced depression-related behavior compared to virgin females, which reminds that 3 days stress may be the threshold of time window for stress induced depressive behaviors in PPD model. The reason for the higher susceptibility to stress of postpartum female mice may be due to the hormonal fluctuations during pregnancy and postpartum [4]. One indication for this is the hypothesis of ovarian-steroid-withdrawal as the cause of postpartum depression [22, 44]. Estrogen levels increase by over 1000-fold shortly before parturition compared to their normal