Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats.
Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats.
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DOI：
10.1016/j.neuropharm.2015.05.012
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发表时间：
2015-10
影响因子：
4.7
通讯作者：
Owens MJ
中科院分区：
文献类型：
--
作者：
Ehrlich DE;Neigh GN;Bourke CH;Nemeth CL;Hazra R;Ryan SJ;Rowson S;Jairam N;Sholar CA;Rainnie DG;Stowe ZN;Owens MJ
怀孕期间的抑郁与宫内压力有关，并与后代的长期症状有关，包括焦虑、无助、注意力缺陷和社交退缩。10%-20%的孕妇被诊断为抑郁症，但抗抑郁药物治疗对后代发育的影响没有很好的记录，特别是对女性。在这里，我们使用了母亲抑郁的产前应激模型来检验宫内抗抑郁药物治疗可以减轻产前应激的影响的假设。我们还研究了产前应激和抗抑郁药物治疗对杏仁核GABA能和5-羟色胺能神经传递相关基因表达的影响，这可能是产前应激行为效应的基础。未分娩的雌性大鼠被植入渗透性微泵，给予临床相关浓度的依西他普兰和交配。怀孕母鼠暴露在12天的混合模式应激源中，并在青春期(出生后28天)和成年(超过90天)对后代进行行为评估，以确定行为变化的程度。我们发现，在子宫应激暴露中，无论埃西普兰治疗如何，青春期女性的焦虑样行为都会增加，并深刻影响调节GABA能功能的氯离子转运体KCC2和NKCC1的表达。相反，出生前单独暴露艾司匹林可增加杏仁核5-HT1a受体的表达。成年后，焦虑样行为恢复到基线水平，杏仁核中的基因表达效应减弱，而孕期暴露于应激下的大鼠出现了新的物体识别缺陷。这些发现表明，产前应激导致女性后代焦虑样行为和杏仁核功能的年龄依赖性缺陷，与抗抑郁药物的暴露无关。
Depression during pregnancy has been linked to in utero stress and is associated with long-lasting symptoms in offspring, including anxiety, helplessness, attentional deficits, and social withdrawal. Depression is diagnosed in 10-20% of expectant mothers, but the impact of antidepressant treatment on offspring development is not well documented, particularly for females. Here, we used a prenatal stress model of maternal depression to test the hypothesis that in utero antidepressant treatment could mitigate the effects of prenatal stress. We also investigated the effects of prenatal stress and antidepressant treatment on gene expression related to GABAergic and serotonergic neurotransmission in the amygdala, which may underlie behavioral effects of prenatal stress. Nulliparous female rats were implanted with osmotic minipumps delivering clinically-relevant concentrations of escitalopram and mated. Pregnant dams were exposed to 12 days of mixed-modality stressors, and offspring were behaviorally assessed in adolescence (postnatal day 28) and adulthood (beyond day 90) to determine the extent of behavioral change. We found that in utero stress exposure, regardless of escitalopram treatment, increased anxiety-like behavior in adolescent females and profoundly influenced amygdala expression of the chloride transporters KCC2 and NKCC1, which regulate GABAergic function. In contrast, prenatal escitalopram exposure alone elevated amygdala expression of 5-HT1A receptors. In adulthood, anxiety-like behavior returned to baseline and gene expression effects in the amygdala abated, whereas deficits emerged in novel object recognition for rats exposed to stress during gestation. These findings suggest prenatal stress causes age-dependent deficits in anxiety-like behavior and amygdala function in female offspring, regardless of antidepressant exposure.