Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada.
Department of Psychology, San Diego State University, San Diego, California.
J Neurophysiol. 2021 Nov 1;126(5):1622-1634. doi: 10.1152/jn.00136.2021. Epub 2021 Sep 8.
Choline is an essential nutrient under evaluation as a cognitive enhancing treatment for fetal alcohol spectrum disorders (FASD) in clinical trials. As a result, there is increased pressure to identify therapeutic mechanism(s) of action. Choline is not only a precursor for several essential cell membrane components and signaling molecules but also has the potential to directly affect synaptic mechanisms that are believed important for cognitive processes. In the current work, we study how the direct application of choline can affect synaptic transmission in the dentate gyrus (DG) of hippocampal slices obtained from adolescent () Sprague-Dawley rats (). The acute administration of choline chloride (2 mM) reliably induced a long-term depression (LTD) of field excitatory postsynaptic potentials (fEPSPs) in the DG in vitro. The depression required the involvement of M1 receptors, and the magnitude of the effect was similar in slices obtained from male and female animals. To further study the impact of choline in an animal model of FASD, we examined offspring from dams fed an ethanol-containing diet (35.5% ethanol-derived calories) throughout gestation. In slices from the adolescent animals that experienced prenatal ethanol exposure (PNEE), we found that the choline induced an LTD that uniquely involved the activation of -methyl-d-aspartate (NMDA) and M1 receptors. This study provides a novel insight into how choline can modulate hippocampal transmission at the level of the synapse and that it can have unique effects following PNEE. Choline supplementation is a nutraceutical therapy with significant potential for a variety of developmental disorders; however, the mechanisms involved in its therapeutic effects remain poorly understood. Our research shows that choline directly impacts synaptic communication in the brain, inducing a long-term depression of synaptic efficacy in brain slices. The depression is equivalent in male and female animals, involves M1 receptors in control animals, but uniquely involves NMDA receptors in a model of FASD.
胆碱作为一种认知增强治疗药物，正在临床试验中评估治疗胎儿酒精谱系障碍（FASD）的效果。因此，人们越来越需要确定其治疗机制。胆碱不仅是几种必需细胞膜成分和信号分子的前体，而且还有可能直接影响突触机制，而这些机制被认为对认知过程很重要。在目前的工作中，我们研究了直接应用胆碱如何影响从青春期（）Sprague-Dawley 大鼠（）获得的海马切片中的齿状回（DG）中的突触传递。胆碱氯化物（2 mM）的急性给药可在体外可靠地诱导 DG 中的长时程抑郁（LTD）。这种抑制需要 M1 受体的参与，并且在来自雄性和雌性动物的切片中，效果的幅度相似。为了在 FASD 的动物模型中进一步研究胆碱的影响，我们检查了在整个妊娠期接受含酒精饮食（35.5％酒精衍生卡路里）的母鼠的后代。在经历过产前乙醇暴露（PNEE）的青春期动物的切片中，我们发现胆碱诱导的 LTD 独特地涉及 -甲基-d-天冬氨酸（NMDA）和 M1 受体的激活。这项研究提供了一个新的见解，即胆碱如何在突触水平调节海马传递，并且在经历过 PNEE 后会产生独特的影响。胆碱补充是一种具有重大潜力的营养疗法，可用于多种发育障碍；但是，其治疗效果所涉及的机制仍知之甚少。我们的研究表明，胆碱直接影响大脑中的突触通讯，在脑片中诱导突触效能的长期抑制。这种抑制在雄性和雌性动物中是等效的，在对照动物中涉及 M1 受体，但在 FASD 模型中则独特地涉及 NMDA 受体。
