Vieiros Melina, Almeida-Toledano Laura, Serra-Delgado Mariona, Navarro-Tapia Elisabet, Ramos-Triguero Anna, Muñoz-Lozano Concha, Martínez Leopoldo, Marchei Emilia, Gómez-Roig María D, García-Algar Óscar, Andreu-Fernández Vicente
Grup de Recerca Infancia i Entorn, Institut d'investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; Spanish network in maternal, neonatal, child, and developmental health research (RICORS-SAMID, RD21/0012/0017, RD24/0013/0019) Instituto de Salud Carlos III, Madrid, Spain; Department de Cirurgia i Especialitats Mèdico-Quirúrgiques, Universitat de Barcelona, Barcelona, Spain.
Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat 08950, Spain; BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine, Hospital Sant Joan de Déu and and Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
Biomed Pharmacother. 2025 Jun;187:118138. doi: 10.1016/j.biopha.2025.118138. Epub 2025 May 10.
Prenatal alcohol exposure (PAE) impairs fetal development leading to fetal alcohol spectrum disorders (FASD). Antioxidants like epigallocatechin-3-gallate (EGCG) may mitigate alcohol-induced oxidative stress, a major contributor to FASD. This study assessed the effects of PAE on cognition and behaviour under two drinking patterns and the role of postnatal EGCG therapy in a FASD-like mouse model. C57BL/6J mice were divided into five groups: control, moderate drinking (Mod), binge drinking (Bin), Mod+EGCG, and Bin+EGCG. Cognitive and behavioural performance were assessed using Rotarod test, T-Maze, and Morris Water Maze (MWM). Western blot analyses evaluated brain and cerebellum biomarkers related to neuronal plasticity, maturation, differentiation, transport, and proliferation. PAE impaired motor coordination, significantly reducing rotarod walking time in both drinking patterns. Spatial learning and memory were also disrupted, decreasing T-maze success rate. It also decreased time in the platform area and distance travelled in MWM. Both drinking patterns affected neuronal plasticity (BDNF, DYRK1A) and maturation (NeuN), astrocyte differentiation (GFAP, s100β), neuronal transport (MBP) and proliferation (GDNF, Wnt-3) via oxidative stress (Nrf2). Our results show how EGCG treatment significantly improved behavioural tests results and restored most brain and cerebellum biomarkers, reaching levels similar to control. These findings highlight the impact of PAE on cognition and behaviour and how EGCG may counteract its effects by reducing oxidative stress and enhancing brain plasticity. Our findings open the door to future studies on the mechanism of action of this antioxidant in order to use it as a therapeutic tool in this vulnerable population.
产前酒精暴露（PAE）会损害胎儿发育，导致胎儿酒精谱系障碍（FASD）。表没食子儿茶素-3-没食子酸酯（EGCG）等抗氧化剂可能会减轻酒精诱导的氧化应激，而氧化应激是FASD的主要促成因素。本研究评估了PAE在两种饮酒模式下对认知和行为的影响，以及产后EGCG治疗在类似FASD的小鼠模型中的作用。将C57BL/6J小鼠分为五组：对照组、适度饮酒组（Mod）、暴饮组（Bin）、Mod+EGCG组和Bin+EGCG组。使用转棒试验、T迷宫和莫里斯水迷宫（MWM）评估认知和行为表现。蛋白质免疫印迹分析评估了与神经元可塑性、成熟、分化、运输和增殖相关的脑和小脑生物标志物。PAE损害了运动协调性，显著缩短了两种饮酒模式下的转棒行走时间。空间学习和记忆也受到干扰，降低了T迷宫成功率。它还减少了在MWM平台区域的停留时间和游动距离。两种饮酒模式均通过氧化应激（Nrf2）影响神经元可塑性（BDNF、DYRK1A）和成熟（NeuN）、星形胶质细胞分化（GFAP、s100β）、神经元运输（MBP）和增殖（GDNF、Wnt-3）。我们的结果表明，EGCG治疗显著改善了行为测试结果，并恢复了大多数脑和小脑生物标志物，使其达到与对照组相似的水平。这些发现突出了PAE对认知和行为的影响，以及EGCG如何通过减少氧化应激和增强脑可塑性来抵消其影响。我们的发现为未来研究这种抗氧化剂的作用机制打开了大门，以便将其用作这一脆弱人群的治疗工具。
