Effects of prenatal dexamethasone on spatial learning and response to stress is influenced by maternal factors

Effects of prenatal dexamethasone on spatial learning and response to stress is influenced by maternal factors
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DOI:
10.1152/ajpregu.2000.279.5.r1899
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发表时间:
2000-11-01
影响因子:
2.8
通讯作者:
Vázquez, DM
Vázquez, DM
中科院分区:
医学3区
文献类型:
--
作者:
Brabham, T;Phelka, A;Vázquez, DM

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本研究调查了产前地塞米松(Dex)暴露对围产期早期事件,海马功能和应激反应的影响。妊娠大鼠从妊娠第15天至分娩期间接受含Dex的晚间水(2.5 μ g/ml)或自来水(Veh)。在分娩当天,将幼仔随机化、交叉饲养,并减少至每只母鼠8或9只。结果分为四组:Veh-Veh(后代在子宫内暴露于Veh,母亲在妊娠期间接受Veh治疗)、Veh-Dex、Dex-Veh和Dex-Dex。采用Morris水迷宫评价空间视觉记忆。采用原位杂交技术检测大鼠海马糖皮质激素受体和盐皮质激素受体mRNA的表达。暴露于地塞米松导致母亲烦躁不安,出生体重低,后代体重增加少。Dex-Dex雄性动物的空间学习能力受损,无法快速终止肾上腺皮质对应激的反应,海马糖皮质激素受体(GR)mRNA表达降低。相比之下,由Veh处理的母亲饲养的Dex暴露动物具有足够的空间学习,增强的糖皮质激素反馈和增加的海马GR mRNA。我们的结论是,在出生后的健康母亲提供的环境可以防止产前地塞米松管理对认知,海马GR mRNA表达和应激反应的质量的不利影响。
The present study investigated the effect of prenatal dexamethasone (Dex) exposure on early perinatal events, hippocampal function, and response to stress. Pregnant rats received Dex in the evening water (2.5 mug/ml) or tap water (Veh) from gestational day 15 until delivery. On the day of parturition, pups were randomized, cross-fostered, and reduced to eight or nine per dam. Four groups resulted: Veh-Veh (offspring exposed to Veh in utero, rearing mother treated with Veh during gestation), Veh-Dex, Dex-Veh, and Dex-Dex. Spatial visual memory was evaluated with the Morris water maze. The corticosterone response to restraint stress was examined, and the expression of hippocampal glucocorticoid and mineralocorticoid receptors mRNA was determined by in situ hybridization. Exposure to Dex caused restlessness in mothers, low birth weights, and poor weight gain in the offspring. The Dex-Dex males had impaired spatial learning, inability to rapidly terminate the adrenocortical response to stress, and decreased hippocampal glucocorticoid receptor (GR) mRNA expression. In contrast, Dex-exposed animals reared by Veh-treated mothers had adequate spatial learning, enhanced glucocorticoid feedback, and increased hippocampal GR mRNA. We conclude that the environment provided by a healthy mother during the postnatal period can prevent the detrimental effects of prenatal Dex administration on cognition, GR mRNA expression of the hippocampus, and the quality of the stress response.