GABA(A)R plasticity during pregnancy: relevance to postpartum depression.
GABA(A)R plasticity during pregnancy: relevance to postpartum depression.
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DOI：
10.1016/j.neuron.2008.06.019
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发表时间：
2008-07-31
期刊：
影响因子：
16.2
通讯作者：
Mody I
中科院分区：
文献类型：
--
作者：
Maguire J;Mody I
Fluctuating neurosteroid levels during the ovarian cycle modulate neuronal excitability through effects on GABAA receptors (GABAARs). The large increase in progesterone-derived neurosteroids during pregnancy and their precipitous decrease at parturition may have considerable effects on GABAARs during pregnancy and postpartum. Here we show a significant decrease in tonic and phasic inhibitions in pregnant mice, mediated by a downregulation of GABAAR δ and γ2 subunits, respectively. This decrease rebounds immediately postpartum. Mice with GABAAR δ subunit deficiencies (Gabrd+/− and Gabrd−/−), in which the rapid postpartum restoration of tonic inhibition is likely to be impaired, exhibit signs of depression-like and abnormal maternal behaviors resulting in reduced pup survival, that were ameliorated in Gabrd+/− mice by a selective agonist (THIP) of GABAARs containing δ subunits. Such mice constitute a novel mouse model of postpartum depression and have great potential for evaluating potential therapeutic interventions.
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