Prevention of alcohol-induced developmental delays and learning abnormalities in a model of fetal alcohol syndrome
Prevention of alcohol-induced developmental delays and learning abnormalities in a model of fetal alcohol syndrome
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DOI：
10.1016/j.ajog.2005.05.052
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发表时间：
2005-09-01
影响因子：
9.8
通讯作者：
Spong, CY
中科院分区：
文献类型：
--
作者：
Endres, M;Toso, L;Spong, CY
目的：产前酒精暴露可导致胎儿死亡和包括学习障碍在内的神经行为并发症。此前，从活性依赖神经营养因子中提取的合成肽已被证明在某些方面可以预防酒精导致的怀孕损伤。本研究的目的是评价活性依赖神经营养因子-12能否预防酒精所致胎儿酒精综合征模型的损伤。研究设计：采用特征明确的模型，C57B16/J小鼠在妊娠第8天分别给予安慰剂、酒精(30%体积/体积酒精0.03毫升/公斤)、酒精加酒精前30分钟的活性依赖神经营养因子-12，或单独给予活性依赖神经营养因子-12。在妊娠第18天评估胎儿死亡率(评估25胎：酒精，n=5；安慰剂，n=9；酒精+活性依赖神经营养因子-12，n=11)。对12只母鼠(酒精16只，安慰剂46只，酒精+活性依赖神经营养因子-12，活性依赖神经营养因子-12，n=35)的后代在出生后第1~21天进行新生儿行为测试。成年男性在Morris水迷宫中接受学习评估，并进行打洞活动测试以进行探索活动。统计分析采用Kruskal-Wallis和方差分析。结果：酒精组胎儿死亡率(67%+/-13%)高于安慰剂组(8.4%+/-3%，P
Objective: Prenatal alcohol exposure results in fetal death and neurobehavioral complications including learning impairment. Previously synthetic peptides derived from activity-dependent neurotrophic factor have been shown to prevent aspects of alcohol-induced damage in pregnancy. The objective of this work was to evaluate whether activity-dependent neurotrophic factor-12 could prevent alcohol-induced damage in a model of fetal alcohol syndrome.Study design: Using a well-characterized model, C57B16/J mice on gestational day 8 were treated with placebo, alcohol (30% volume/volume alcohol 0.03 mL/kg), alcohol plus activity-dependent neurotrophic factor-12 30 minutes prior to alcohol, or activity-dependent neurotrophic factor-12 alone. Fetal death was assessed on gestational day 18 (25 litters were evaluated: alcohol, n = 5; placebo, n = 9; alcohol plus activity-dependent neurotrophic factor-12, n = 11). Neonatal behavior tests were performed on postnatal days 1 through 21 with the offspring of 12 dams (alcohol, n = 16; placebo, n = 46; alcohol plus activity-dependent neurotrophic factor-12, n = 23; and activity-dependent neurotrophic factor-12, n = 35). Adult males were tested in the Morris water maze for learning assessment and with the hole punch activity test for exploratory activity. Statistical analysis included Kruskal-Wallis and analysis of variance.Results: Fetal death was greater in alcohol (67% +/- 13%) vs placebo (8.4% +/- 3%, P