Choline supplementation attenuates learning deficits associated with neonatal alcohol exposure in the rat: effects of varying the timing of choline administration.
Choline supplementation attenuates learning deficits associated with neonatal alcohol exposure in the rat: effects of varying the timing of choline administration.
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DOI：
10.1016/j.brainres.2008.08.048
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发表时间：
2008-10-27
期刊：
影响因子：
2.9
通讯作者：
Thomas JD
中科院分区：
文献类型：
--
作者：
Ryan SH;Williams JK;Thomas JD
尽管胎儿酒精暴露的有害影响，一些孕妇继续饮酒。因此，必须寻求安全，有效的治疗胎儿酒精谱系障碍的儿童。使用动物模型，我们的实验室已经证明，胆碱，一种必需的营养素，有效地降低了一些胎儿酒精影响的严重程度，即使在乙醇损伤完成后给药。本研究调查是否有一个关键的发展时期时，胆碱是最有效的衰减乙醇的致畸作用。Sprague-Dawley大鼠在妊娠晚期脑生长突增期（出生后第4-9天）通过插管暴露于5.25 g/kg/天乙醇。包括非插管对照组和假插管对照组。在乙醇暴露后，幼仔从PD 11-20、PD 21-30或PD 11-30接受生理盐水溶剂或氯化胆碱（100 mg/kg/天）皮下注射。从PD 45开始，对受试者进行Morris水迷宫空间学习任务测试。与对照组相比，未接受胆碱的乙醇暴露组和接受PD 21-30胆碱处理的乙醇暴露组在获取Morris水迷宫任务期间的表现显著受损。用来自PD 11-20或PD 11-30的胆碱处理的乙醇暴露组的性能是中等的，与任何其他组没有显著差异。然而，在探测试验中，乙醇暴露产生了显着的空间记忆缺陷，缓解了所有胆碱治疗，无论管理的时间。这些发现表明，胆碱的治疗窗口可能非常大，或者跨越本研究中研究的两个发育时期。重要的是，这些研究结果表明，胆碱补充剂可以有效地减少一些与酒精相关的学习障碍，即使在儿童后期服用。
Despite the harmful effects of fetal alcohol exposure, some pregnant women continue to drink alcohol. Thus, it is imperative to pursue safe, effective treatments for children with fetal alcohol spectrum disorders. Using an animal model, our laboratory has demonstrated that choline, an essential nutrient, effectively reduces the severity of some fetal alcohol effects, even when administered after the ethanol insult is complete. The present study investigated whether there is a critical developmental period when choline is most effective in attenuating ethanol’s teratogenic effects. Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol during the third trimester equivalent brain growth spurt (postnatal days (PD) 4–9) via intubation. A non-intubation control group and a sham intubation control group were included. Following ethanol exposure, pups received subcutaneous injections of saline vehicle or choline chloride (100 mg/kg/day) from PD 11–20, PD 21–30, or PD 11–30. Beginning on PD 45, subjects were tested on a Morris water maze spatial learning task. Performance of both the ethanol-exposed group that did not receive choline and the ethanol-exposed group treated with choline from PD 21–30 was significantly impaired compared to controls during acquisition of the Morris water maze task. Performance of ethanol-exposed groups treated with choline from PD 11–20 or PD 11–30 was intermediate, not differing significantly from any other groups. However, during the probe trial, ethanol exposure produced significant deficits in spatial memory which were mitigated by all choline treatments, regardless of the timing of administration. These findings suggest that choline’s therapeutic window may be very large, or spans across the two developmental periods examined in this study. Importantly, these findings indicate that choline supplementation may effectively reduce some alcohol-related learning impairments, even when administered in later childhood.
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