Postpartum estrogen withdrawal impairs GABAergic inhibition and LTD induction in basolateral amygdala complex via down-regulation of GPR30
Postpartum estrogen withdrawal impairs GABAergic inhibition and LTD induction in basolateral amygdala complex via down-regulation of GPR30
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DOI：
10.1016/j.euroneuro.2017.05.010
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发表时间：
2017-08
影响因子：
5.6
通讯作者：
Rong Yang;Baofeng Zhang;Tingting Chen;Suyun Zhang;Ling Chen
中科院分区：
文献类型：
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作者：
Rong Yang;Baofeng Zhang;Tingting Chen;Suyun Zhang;Ling Chen
产后雌激素（E2）停药是已知的抑郁症状的一个特别脆弱的时间。在这项研究中，卵巢切除（OVX）小鼠与苯甲酸雌二醇和孕酮（E2/P4）的共同管理，然后管理E2单独（E2）和随后的E2撤药（EW），以模拟怀孕期间和产后的激素变化。本研究旨在探讨模拟妊娠后撤除雌二醇对基底外侧杏仁核复合体（BLA）突触功能和可塑性的影响。与对照组小鼠相比，EW小鼠在旷场试验的中心部分和高架十字迷宫的开放臂中花费的时间更少。兴奋性突触后电位（EPSP）的斜率在E2/P4-小鼠的外囊BLA突触减少，恢复E2-小鼠，并增加EW-小鼠。EW-小鼠表现出EPSP持续时间和配对脉冲抑制（PPI）的显著增加，EPSP的多峰反应和长期抑郁（LTD）诱导的损害，这被GABAAR激动剂蝇蕈醇纠正。雌激素受体（ER）GPR 30、ERα和ERβ在EW小鼠BLA中的表达水平均低于对照组。将GPR 30激动剂G-1应用于EW小鼠的BLA中，可恢复GABAAR介导的抑制和LTD指示，但ERβ激动剂DPN或ERα激动剂PPT不能。单次注射G-1而非DPN或PPT可部分缓解EW小鼠的焦虑样行为。结果表明，产后E2戒断通过降低GPR 30表达，导致BLA中GABAAR介导的抑制功能障碍，从而削弱LTD诱导并引起焦虑样行为。
Postpartum estrogen (E2) withdrawal is known to be a particularly vulnerable time for depressive symptoms. In this study, ovariectomized (OVX) mice were treated with co-administration of estradiol benzoate and progesterone (E2/P4) followed by administration of E2 alone (E2) and a subsequent E2 withdrawal (EW) to mimic the hormonal changes during pregnancy and postpartum. The objective of this study was to investigate the influence of E2 withdrawal after hormone-simulated pregnancy on synaptic function and plasticity in basolateral amygdala complex (BLA). In comparison to control mice, EW mice spent less time in the central portion of open-field test and open arms of elevated plus-maze. Excitatory postsynaptic potentials (EPSPs) slopes at external capsule BLA synapse were reduced in E2/P4-mice, recovered in E2-mice, and increased in EW-mice. EW-mice showed a significant increase in duration of EPSPs and paired-pulse inhibition (PPI) with multi-spike responses of EPSPs and impairment of long-term depression (LTD) induction, which were corrected by GABAAR agonist muscimol. Levels of estrogen receptor (ER) GPR30, ERα and ERβ expression in BLA of EW-mice were lower than those in control mice. The bath-application of GPR30 agonist G-1 in BLA of EW-mice recovered the GABAAR-mediated inhibition and LTD indication, but ERβ agonist DPN or ERα agonist PPT could not. A single BLA-injection of G-1 rather than DPN or PPT in EW-mice could partially relieve the anxiety-like behaviors. The results indicate that postpartum E2 withdrawal causes dysfunction of GABAAR-mediated inhibition in the BLA through reducing GPR30 expression, which impairs LTD induction and causes anxiety-like behaviors.