Division of Medical Sciences, University of Victoria, Victoria, BC V8W 2Y2, Canada.
Department of Psychology, San Diego State University, San Diego, CA 92120, USA.
Nutrients. 2022 May 10;14(10):2004. doi: 10.3390/nu14102004.
Prenatal ethanol exposure (PNEE) is a leading cause of neurodevelopmental impairments, yet treatments for individuals with PNEE are limited. Importantly, postnatal supplementation with the essential nutrient choline can attenuate some adverse effects of PNEE on cognitive development; however, the mechanisms of action for choline supplementation remain unclear. This study used an animal model to determine if choline supplementation could restore hippocampal synaptic plasticity that is normally impaired by prenatal alcohol. Throughout gestation, pregnant Sprague Dawley rats were fed an ethanol liquid diet (35.5% ethanol-derived calories). Offspring were injected with choline chloride (100 mg/kg/day) from postnatal days (PD) 10-30, and then used for in vitro electrophysiology experiments as juveniles (PD 31-35). High-frequency conditioning stimuli were used to induce long-term potentiation (LTP) in the medial perforant path input to the dentate gyrus of the hippocampus. PNEE altered synaptic transmission in female offspring by increasing excitability, an effect that was mitigated with choline supplementation. In contrast, PNEE juvenile males had decreased LTP compared to controls, and this was rescued by choline supplementation. These data demonstrate sex-specific changes in plasticity following PNEE, and provide evidence that choline-related improvements in cognitive functioning may be due to its positive impact on hippocampal synaptic physiology.
产前乙醇暴露（PNEE）是神经发育障碍的主要原因，但针对 PNEE 个体的治疗方法有限。重要的是，产后补充必需营养素胆碱可以减轻 PNEE 对认知发育的一些不利影响；然而，胆碱补充的作用机制仍不清楚。本研究使用动物模型来确定胆碱补充是否可以恢复海马突触可塑性，而这种可塑性通常会被产前酒精损害。在整个孕期，怀孕的 Sprague Dawley 大鼠喂食含乙醇的液体饮食（35.5%由乙醇衍生的卡路里）。后代从出生后第 10 天到第 30 天每天注射氯化胆碱（100mg/kg），然后在幼年期（出生后第 31-35 天）用于体外电生理学实验。高频条件刺激用于诱导海马齿状回内的中隔穿通路径输入的长时程增强（LTP）。PNEE 通过增加兴奋性改变了雌性后代的突触传递，胆碱补充减轻了这种影响。相比之下，PNEE 幼鼠雄性的 LTP 低于对照组，胆碱补充可挽救这一现象。这些数据表明 PNEE 后存在性别特异性的可塑性变化，并提供证据表明胆碱相关的认知功能改善可能是由于其对海马突触生理学的积极影响。
