Postpartum depression (PPD) is a serious psychiatric disorder, affecting not only the childbearing women but also the health of their offsprings. The brain-derived neurotrophic factor (Bdnf) gene is an important target gene for the study of depression and antidepressant therapy. FoxO1, belonging to the FoxO subfamily is involved in the development of major depressive disorders. However, the role of BDNF and its functional brain regions involved in PPD remains unknown. Here, we report that chronic unpredictable stress (CUS) can produce depression-associated behaviors in postpartum female mice. CUS can decrease total Bdnf mRNA and exon specific mRNAs in the medial prefrontal cortex (mPFC), accompanied by reduced protein levels, that were correlated with depression-related behaviors. Moreover, postpartum, not virgin female mice showed increased susceptibility to subthreshold stress-induced depression-related behaviors. Selective deletion of BDNF in the mPFC induced anhedonia as indicated by reduced sucrose preference and increased latency to food in the novelty suppressed food test in postpartum, but not in virgin female mice. Furthermore, we found that FoxO1 is also decreased in CUS-treated postpartum female mice with a significant correlation with depression-related behaviors. BDNF-specific knockout in the mPFC decreased FoxO1 expression in female mice. Our results indicate that the BDNF-FoxO1 axis in mPFC can regulate depression-related behaviors and stress vulnerability in postpartum female mice.

中文翻译：

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内侧前额叶皮质中的 BDNF-FoxO1 轴调节产后雌性小鼠由慢性不可预测压力引起的抑郁样行为。


产后抑郁症（PPD）是一种严重的精神疾病，不仅影响育龄妇女，而且影响其后代的健康。脑源性神经营养因子（Bdnf）基因是抑郁症和抗抑郁治疗研究的重要靶基因。 FoxO1 属于 FoxO 亚家族，与重度抑郁症的发展有关。然而，BDNF 及其参与 PPD 的功能性大脑区域的作用仍不清楚。在这里，我们报告慢性不可预测压力（CUS）可以在产后雌性小鼠中产生与抑郁相关的行为。 CUS 可以减少内侧前额皮质 (mPFC) 中的总 Bdnf mRNA 和外显子特异性 mRNA，同时降低与抑郁相关行为相关的蛋白质水平。此外，产后而非处女的雌性小鼠对阈下压力诱发的抑郁相关行为的敏感性增加。在产后新奇抑制食物测试中，mPFC 中 BDNF 的选择性缺失会诱导快感缺失，如蔗糖偏好减少和食物潜伏期增加，但在处女雌性小鼠中则不然。此外，我们发现接受 CUS 治疗的产后雌性小鼠中 FoxO1 也有所减少，与抑郁相关行为显着相关。 mPFC 中 BDNF 特异性敲除降低了雌性小鼠 FoxO1 的表达。我们的结果表明，mPFC 中的 BDNF-FoxO1 轴可以调节产后雌性小鼠的抑郁相关行为和应激脆弱性。