Department of Neurology, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, 212001, PR China; School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, 212013, PR China.
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, 212013, PR China; Changzhou Children's Hospital, Changzhou, Jiangsu Province, 213003, PR China.
Biochem Biophys Res Commun. 2020 Feb 26;523(1):159-164. doi: 10.1016/j.bbrc.2019.12.040. Epub 2019 Dec 11.
Although postpartum depression (PPD) is the leading cause of disability worldwide, its molecular mechanisms are poorly understood. Recent evidence has suggested that impaired glucocorticoid receptor (GR), the signaling of key molecules of the HPA axis, plays a key role in the behavioral and neuroendorcrine alterations of major depression. However, the role of GR in postpartum period, which following with the abrupt withdrawal of placental corticotropin releasing hormone (CRH) and resulting in a re-equilibration of the maternal HPA axis in the days of post-delivery, is still not entirely clear. Previously, a hormone-simulated pregnancy (HSP), and the subsequent 'postpartum' withdrawal in estrogen has been employed to mimic the fluctuations in estradiol associated with pregnancy and postpartum. Using the HSP model, we investigated here the effect of 'postpartum' withdrawal in estrogen as well as depression- and anxiety-like behavior by intra-hippocampal infusion with GR inhibitor-RU486. Following the successful acquisition of PPD model by withdrawal in estrogen, reduced GR expression was observed in hippocampus. Further, HSP-rats suffered intra-hippocampal RU486 infusion presented depression- and anxiety-like behavior as postpartum depression. Together, these results suggest an important, though complex, role for GR in the behavioral regulation of postpartum depression.
虽然产后抑郁症（PPD）是全球导致残疾的主要原因，但它的分子机制仍不清楚。最近的证据表明，糖皮质激素受体（GR）受损，即 HPA 轴关键分子的信号转导，在重度抑郁症的行为和神经内分泌改变中起着关键作用。然而，GR 在产后期间的作用，产后期间胎盘促肾上腺皮质激素释放激素（CRH）的突然撤出，导致母体 HPA 轴在产后数天内重新平衡，仍然不完全清楚。以前，激素模拟妊娠（HSP），以及随后雌激素的“产后”撤出，已被用于模拟与妊娠和产后相关的雌二醇波动。使用 HSP 模型，我们通过向海马内输注 GR 抑制剂 RU486 来研究雌激素撤出以及抑郁和焦虑样行为的影响。在成功建立雌激素撤出的 PPD 模型后，在海马中观察到 GR 表达减少。此外，HSP 大鼠接受海马内 RU486 输注后表现出产后抑郁症的抑郁和焦虑样行为。总之，这些结果表明 GR 在产后抑郁症的行为调节中起着重要但复杂的作用。
