Iqbal U, Brien J F, Banjanin S, Andrews M H, Matthews S G, Reynolds J N
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
J Neuroendocrinol. 2005 Sep;17(9):600-8. doi: 10.1111/j.1365-2826.2005.01349.x.
The present study tested the hypothesis that chronic prenatal ethanol exposure causes long-lasting changes in glucocorticoid signalling in postnatal offspring. Pregnant guinea pigs were treated with ethanol (4 g/kg maternal body weight/day), isocaloric-sucrose/pair-feeding or water throughout gestation, and maternal saliva cortisol concentration was determined 2 h after treatment at different stages of gestation. Electrically-stimulated release of glutamate and GABA, in the presence or absence of dexamethasone, as well as glucocorticoid and mineralocorticoid receptor mRNA expression, was determined in the hippocampus and prefrontal cortex of adult offspring of treated pregnant guinea pigs. Maternal saliva cortisol concentration increased throughout pregnancy, which was associated with increased foetal plasma and amniotic fluid cortisol concentration. Ethanol administration to pregnant guinea pigs increased maternal saliva cortisol concentration during early and mid-gestation. In late gestation, ethanol administration did not increase saliva cortisol concentration above that induced by pregnancy. Chronic prenatal ethanol exposure had no effect on stimulated glutamate or GABA release, but selectively prevented dexamethasone-mediated suppression of stimulated glutamate release, and decreased expression of mineralocorticoid, but not glucocorticoid, receptor mRNA in the hippocampus of adult offspring. These data indicate that maternal ethanol administration leads to excessively increased maternal cortisol concentration that can impact negatively the developing foetal brain, leading to persistent postnatal deficits in glucocorticoid regulation of glutamate signalling in the adult hippocampus.
孕期长期暴露于乙醇会导致出生后子代的糖皮质激素信号传导发生持久变化。在整个妊娠期，对怀孕的豚鼠分别给予乙醇（4克/千克母体体重/天）、等热量蔗糖/配对喂养或水，并在妊娠不同阶段给药后2小时测定母体唾液皮质醇浓度。在接受处理的怀孕豚鼠的成年子代的海马体和前额叶皮质中，测定在有或没有地塞米松存在的情况下谷氨酸和γ-氨基丁酸的电刺激释放，以及糖皮质激素和盐皮质激素受体mRNA表达。整个孕期母体唾液皮质醇浓度升高，这与胎儿血浆和羊水皮质醇浓度升高有关。给怀孕豚鼠施用乙醇会在妊娠早期和中期增加母体唾液皮质醇浓度。在妊娠晚期，施用乙醇并未使唾液皮质醇浓度升高至高于妊娠诱导的水平。孕期长期暴露于乙醇对刺激的谷氨酸或γ-氨基丁酸释放没有影响，但选择性地阻止了地塞米松介导的对刺激的谷氨酸释放的抑制，并降低了成年子代海马体中盐皮质激素而非糖皮质激素受体mRNA的表达。这些数据表明，母体施用乙醇会导致母体皮质醇浓度过度升高，这可能会对发育中的胎儿大脑产生负面影响，导致成年海马体中谷氨酸信号的糖皮质激素调节在出生后持续存在缺陷。
