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孕期γ-氨基丁酸A型受体可塑性：与产后抑郁的相关性

GABA(A)R plasticity during pregnancy: relevance to postpartum depression.

作者信息

Maguire Jamie, Mody Istvan

机构信息

Department of Neurology, The David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

出版信息

Neuron. 2008 Jul 31;59(2):207-13. doi: 10.1016/j.neuron.2008.06.019.

DOI:10.1016/j.neuron.2008.06.019
PMID:18667149
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2875248/
Abstract

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.

摘要

在卵巢周期中波动的神经甾体水平通过对γ-氨基丁酸A型受体（GABA(A)Rs）的作用来调节神经元兴奋性。孕期孕酮衍生的神经甾体大幅增加，而在分娩时急剧下降，这可能在孕期和产后对GABA(A)Rs产生相当大的影响。在此我们表明，妊娠小鼠的紧张性和相位性抑制显著降低，分别由GABA(A)R δ和γ2亚基的下调介导，产后立即反弹。在整个孕期不表现出GABA(A)R δ亚基调节的小鼠（Gabrd(+/-)和Gabrd(-/-)）表现出抑郁样和异常的母性行为，导致幼崽存活率降低。在Gabrd(+/-)小鼠中，一种GABA(A)R δ亚基选择性激动剂THIP改善了这些异常的产后行为。我们认为，Gabrd(+/-)和Gabrd(-/-)小鼠构成了产后抑郁症的小鼠模型，可能有助于评估潜在的治疗干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d0b/2875248/e2b09dbec3cf/nihms-203995-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d0b/2875248/94e91be93799/nihms-203995-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d0b/2875248/622b6bbc088d/nihms-203995-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d0b/2875248/c6a072d71bb4/nihms-203995-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d0b/2875248/e2b09dbec3cf/nihms-203995-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d0b/2875248/94e91be93799/nihms-203995-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d0b/2875248/622b6bbc088d/nihms-203995-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d0b/2875248/c6a072d71bb4/nihms-203995-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d0b/2875248/e2b09dbec3cf/nihms-203995-f0004.jpg

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