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首页> 外文期刊>Neuron >GABA(A)R plasticity during pregnancy: relevance to postpartum depression.
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GABA(A)R plasticity during pregnancy: relevance to postpartum depression.

机译：怀孕期间的GABA（A）R可塑性：与产后抑郁症的相关性。

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摘要

Fluctuating neurosteroid levels over the ovarian cycle modulate neuronal excitability through effects on GABA(A) receptors (GABA(A)Rs). The large increase in progesterone-derived neurosteroids during pregnancy and their precipitous decline at parturition may have considerable effects on GABA(A)Rs during pregnancy and postpartum. Here we show a significant decrease in tonic and phasic inhibitions in pregnant mice, mediated by a downregulation of GABA(A)R delta and gamma2 subunits, respectively, which rebounds immediately postpartum. Mice which do not exhibit GABA(A)R delta subunit regulation throughout pregnancy (Gabrd(+/-) and Gabrd(-/-)) exhibit depression-like and abnormal maternal behaviors, resulting in reduced pup survival. These abnormal postpartum behaviors were ameliorated in Gabrd(+/-) mice by a GABA(A)R delta-subunit-selective agonist, THIP. We suggest that Gabrd(+/-) and Gabrd(-/-) mice constitute a mouse model of postpartum depression that may be useful for evaluating potential therapeutic interventions.
机译：卵巢周期中神经甾体水平的波动通过对GABA（A）受体（GABA（A）Rs）的影响来调节神经元兴奋性。孕期孕激素衍生的神经类固醇大量增加，并且在分娩时急剧下降，可能对孕期和产后的GABA（A）Rs产生很大影响。在这里，我们显示了妊娠小鼠的强直和阶段性抑制作用的显着降低，分别由下调的GABA（A）Rδ和gamma2亚基介导，其在产后立即反弹。在整个怀孕期间未表现出GABA（A）Rδ亚基调控的小鼠（Gabrd（+/-）和Gabrd（-/-））表现出抑郁样和异常的母性行为，从而导致幼崽存活率降低。通过GABA（A）Rδ亚基选择性激动剂THIP，在Gabrd（+/-）小鼠中改善了这些异常的产后行为。我们建议Gabrd（+/-）和Gabrd（-/-）小鼠构成产后抑郁症的小鼠模型，可能对评估潜在的治疗干预措施有用。

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