Fetal Alcohol Effects and Choline Intervention

父母饮酒会导致中枢神经系统功能障碍和行为改变。尽管这些行为变化有很好的特征，但对减少这些影响的有效干预措施知之甚少。许多与产前酒精暴露相关的行为缺陷（如多动症和记忆问题）与中隔海马胆碱能系统的损害是一致的。有趣的是，数据表明，围产期补充胆碱会对胆碱能功能产生持久的改变，并在治疗期后改善学习能力。我们最近证明，父母酒精伤害后的围产期胆碱可以减轻乙醇的一些不良行为影响，这表明补充胆碱可能是治疗酒精引起的行为障碍的潜在方法。本项目探讨胆碱在减轻发育性酒精治疗对行为和胆碱能测量的影响方面的能力。首先，为了确定胆碱作用的任务特异性，将对几个任务的表现进行检查。还将测试胆碱给药的剂量和时间参数。其次，为了确定行为改变是否与胆碱能功能的改变有关，围产期补充胆碱对胆碱能系统的影响也将被检查。最后，将检测神经生长因子水平，以确定这是否可能是胆碱改变大脑和行为发育的一种机制。FAS研究的一个高度优先事项是确定相关行为问题的干预措施。该建议提出了一种基于酒精暴露动物胆碱能功能缺陷的可能干预措施。由于围产期补充胆碱对胆碱能系统和行为有持久的影响，这种治疗可能减轻产前酒精暴露的影响。确定有效的饮食干预对产前暴露于酒精的儿童具有重要意义。

Parental alcohol produces CNS dysfunction and behavioral alterations. Although these behavioral changes are well-characterized, little is known about effective interventions to reduce these effects. Many behavioral deficits associated with prenatal alcohol exposure (e.g. hyperactivity and memory problems) are consistent with damage to the septohippocampal cholinergic system. Interestingly, data suggest that perinatal choline supplementation produces long-lasting alterations in cholinergic functioning and improves learning well beyond the treatment period. We recently demonstrated that perinatal choline following a parental alcohol insult mitigates some of ethanol's adverse behavioral effects, indicating that the choline supplementation might be potential treatment for alcohol- induced behavioral dysfunction. This project examines the ability of choline to attenuate the effects of developmental alcohol treatment on behavioral and cholinergic measures. First, to determine the task-specificity of choline's effects, performance on several tasks will be examined. Dose and timing parameters of choline administration will also be tested. Secondly, to determine if behavioral changes are related to changes in the cholinergic functioning, the effects of perinatal choline supplementation on cholinergic systems will also be examined. Finally, NGF levels will be examined to determine if this might br one mechanism by which choline alters brain and behavioral development. A high priority in FAS research is the identification of interventions for the associated behavioral problems. This proposal addresses one possible intervention based upon a deficit in cholinergic functioning in alcohol-exposed animals. Since perinatal choline supplementation has long-lasting effects on the cholinergic system and behavior, this treatment might mitigate the effects of prenatal alcohol exposure. The identification of an effective dietary intervention has important implications for children exposed to alcohol prenatally.