Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study, Panjab University, Chandigarh, India.
Int J Neuropsychopharmacol. 2010 Sep;13(8):1053-66. doi: 10.1017/S146114571000060X. Epub 2010 Jun 9.
Clinical and experimental evidence has demonstrated that ethanol is a teratogen, and its consumption during pregnancy induces harmful effects on the developing fetus that leads to mental retardation and long-term cognitive and behavioural deficits in offspring. The brain growth spurt period is highly sensitive to the neurotoxic effects of ethanol and it corresponds to the last trimester in humans and the first two postnatal weeks in rodents. This study was designed to evaluate the effect of epigallocatechin-3-gallate (EGCG) on alcohol-induced behavioural, biochemical and molecular changes in rat pups. Pups were administered alcohol (5 g/kg, 12% v/v) by intragastric intubation on postnatal days (PD) 7, 8, and 9. Ethanol-exposed pups showed impaired spatial navigation in the Morris water maze test and poor retention in the elevated plus maze task conducted from PD 24 to 28 which was coupled with enhanced acetylcholinesterase activity, increased oxidative-nitrosative stress, cytokines (TNF-alpha and IL-1beta), NF-kappaB and caspase-3 levels in both the cortex and hippocampus of pups sacrificed at PD 28. Apart from this, the mean weight of the whole brain, cortex and hippocampus of ethanol-treated pups was decreased by 34.48%, 39.09% and 34.30%, respectively. EGCG (50 and 100 mg/kg) significantly attenuated all the behavioural, biochemical and molecular changes in the different brain regions of ethanol-treated pups. The current finding demonstrates the activation of oxidative-nitrosative stress-mediated apoptotic signalling in cognitive deficits associated with fetal alcohol spectrum disorders (FASDs) and suggests that EGCG may have potential in prevention of the cognitive impairment in children with FASDs.
临床和实验证据表明，乙醇是一种致畸物，其在怀孕期间的摄入会对发育中的胎儿产生有害影响，导致后代智力迟钝和长期认知及行为缺陷。大脑生长突增期对乙醇的神经毒性作用高度敏感，它对应于人类的最后一个 trimester 和啮齿动物的出生后前两周。本研究旨在评估表没食子儿茶素没食子酸酯（EGCG）对酒精诱导的幼鼠行为、生化和分子变化的影响。幼鼠在出生后第 7、8 和 9 天通过胃内插管给予酒精（5 g/kg，12%v/v）。酒精暴露的幼鼠在 Morris 水迷宫测试中表现出空间导航受损，在 PD24 至 28 进行的高架十字迷宫任务中保留能力差，这与乙酰胆碱酯酶活性增强、氧化应激增加、细胞因子（TNF-α和 IL-1β）、NF-κB 和 caspase-3 水平升高有关大脑皮质和海马组织中幼鼠在 PD28 处死时。除此之外，乙醇处理的幼鼠的整个大脑、皮质和海马体的平均重量分别降低了 34.48%、39.09%和 34.30%。EGCG（50 和 100mg/kg）显著减轻了乙醇处理幼鼠不同脑区的所有行为、生化和分子变化。目前的发现表明，氧化应激介导的细胞凋亡信号通路在与胎儿酒精谱系障碍（FASD）相关的认知缺陷中被激活，并表明 EGCG 可能具有预防 FASD 儿童认知障碍的潜力。
