A postpartum model in rat: Behavioral and gene expression changes induced by ovarian steroid deprivation
A postpartum model in rat: Behavioral and gene expression changes induced by ovarian steroid deprivation
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DOI：
10.1016/j.biopsych.2008.03.029
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发表时间：
2008-08-15
影响因子：
10.6
通讯作者：
Duman, Ronald S.
中科院分区：
文献类型：
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作者：
Suda, Shiro;Segi-Nishida, Eri;Duman, Ronald S.
背景：产后抑郁(PPD)在产后4周内影响大约10%-20%的妇女，其特征是情绪不稳定，突出的焦虑和易怒，失眠和抑郁情绪。在产后期间，升高的卵巢激素突然下降到卵泡期的早期水平，这被认为是触发PPD的主要作用。然而，导致产后抑郁的潜在神经生物学机制尚未确定。方法：在本研究中，我们研究了卵巢类固醇对大鼠行为和基因表达的影响。在本研究中，卵巢类固醇的水平发生在人怀孕期间，然后快速停药以模拟产后条件。结果：行为测试结果显示，激素模拟产后治疗导致与产后抑郁相关的表型的发展，包括易感无助、增加焦虑和攻击性。实时定量聚合酶链式反应(PCR)显示了几个基因的瞬时调节，包括钙/钙调素依赖的蛋白激酶II(CaMKII)、5-羟色胺转运体(SERT)、肌细胞增强因子2A(MEF2A)、脑源性神经营养因子(BDNF)、γ-氨基丁酸A型受体α4(GABAARA4)、母亲抗十面瘫同系物4(Smad4)和水通道4(AQP4)。结论：这些研究为进一步了解高剂量卵巢激素对行为的影响和脑内基因表达的病理变化提供了可能。
Background: Postpartum depression (PPD) affects approximately 10% to 20% of women during the first 4 weeks of the postpartum period and is characterized by labile mood with prominent anxiety and irritability, insomnia, and depressive mood. During the postpartum period, elevated ovarian hormones abruptly decrease to the early follicular phase levels that are postulated to play a major role in triggering PPD. However, the underlying neurobiological mechanisms that contribute to PPD have not been determined.Methods: In the present study, we examined the effect of ovarian steroids, administered at levels that occur during human pregnancy followed by rapid withdrawal to simulate postpartum conditions, on behavior and gene expression in the rat.Results: The results of behavioral testing reveal that the hormone-simulated postpartum treatment results in the development of a phenotype relevant to PPD, including vulnerability for helplessness, increased anxiety, and aggression. Real-time quantitative polymerase chain reaction (PCR) demonstrated transient regulation of several genes, including Ca2+/calmodulin-dependent protein kinase II (CAMKII), serotonin transporter (SERT), myocyte enhancer factor 2A (MEF2A), brain-derived neurotrophic factor (BDNF), gamma-aminobutyric acid type A receptor alpha 4 (GABAARA4), mothers against decapentaplegic homolog 4 (SMAD4), and aquaporin 4 (AQP4) that could underlie these behavioral effects.Conclusions: These studies provide an improved understanding of the effects of withdrawal from high doses of ovarian hormones on behavior and gene expression changes in the brain that could contribute to the pathophysiology of PPD.