Perinatal choline supplementation attenuates behavioral alterations associated with neonatal alcohol exposure in rats

Perinatal choline supplementation attenuates behavioral alterations associated with neonatal alcohol exposure in rats
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DOI:
10.1016/j.ntt.2003.10.002
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发表时间:
2004-01-01
影响因子:
2.9
通讯作者:
O'Neill, TM
O'Neill, TM
中科院分区:
医学3区
文献类型:
--
作者:
Thomas, JD;Garrison, M;O'Neill, TM

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产前接触酒精的儿童会出现各种行为改变,包括多动症和学习障碍。鉴于妇女在怀孕期间继续饮酒,确定有效的干预和治疗至关重要。以前,我们曾报道,出生后早期补充胆碱可以降低产前暴露于酒精的大鼠学习障碍的严重程度。本研究旨在探讨是否胆碱补充剂可以减少与酒精暴露相关的行为改变的严重程度在孕晚期相当于大脑生长突增。将雄性新生大鼠分配至三个给药组之一。一组通过人工饲养程序从出生后(PD)4-9天暴露于酒精(6.6 g/kg/天)。包括牺牲饲养和正常饲养的对照组。每种治疗的一半受试者从PD 4-30开始每天接受氯化胆碱溶液皮下注射,而另一半接受生理盐水溶媒注射。在PD 31-34,胆碱治疗完成后,监测活动水平,并在PD 40-42,受试者进行了一系列空间辨别逆转学习任务的测试。与对照组相比,暴露于酒精的受试者明显过度活跃。乙醇诱导的多动症的严重程度与胆碱治疗减弱。此外,受试者暴露于乙醇在新生儿期犯了显着更多的持续型错误的逆转学习任务相比,控制。暴露于胆碱显着减少乙醇相关的错误的数量。重要的是,这些行为变化不是由于胆碱的急性效应,而是与早期补充胆碱的长期组织效应有关。这些数据表明,早期饮食干预可能会降低胎儿酒精影响的严重程度。(C)2003年爱思唯尔公司All rights reserved.
Children exposed to alcohol prenatally suffer from a variety of behavioral alterations, including hyperactivity and learning deficits. Given that women continue to drink alcohol during pregnancy, it is critical that effective interventions and treatments be identified. Previously, we reported that early postnatal choline supplementation can reduce the severity of learning deficits in rats exposed to alcohol prenatally. The present study examined whether choline supplementation can reduce the severity of behavioral alterations associated with alcohol exposure during the third trimester equivalent brain growth spurt. Male neonatal rats were assigned to one of three treatment groups. One group was exposed to alcohol (6.6 g/kg/day) from postnatal days (PD) 4-9 via an artificial rearing procedure. Artificially reared and normally reared control groups were included. One half of subjects from each treatment received daily subcutaneous injections of a choline chloride solution from PD 4-30, whereas the other half received saline vehicle injections. On PD 31-34, after choline treatment was complete, activity level was monitored and, on PD 40-42, subjects were tested on a serial spatial discrimination reversal learning task. Subjects exposed to alcohol were significantly hyperactive compared to controls. The severity of ethanol-induced hyperactivity was attenuated with choline treatment. In addition, subjects exposed to ethanol during the neonatal period committed a significantly greater number of perseverative-type errors on the reversal learning task compared to controls. Exposure to choline significantly reduced the number of ethanol-related errors. Importantly, these behavioral changes were not due to the acute effects of choline, but were related to long-lasting organizational effects of early choline supplementation. These data suggest that early dietary interventions may reduce the severity of fetal alcohol effects. (C) 2003 Elsevier Inc. All rights reserved.