Brocardo Patricia S, Gil-Mohapel Joana, Wortman Ryan, Noonan Athena, McGinnis Eric, Patten Anna R, Christie Brian R
Division of Medical Sciences and UBC Island Medical Program , University of Victoria, Victoria, British Columbia, Canada.
Department of Morphological Sciences, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
Alcohol Clin Exp Res. 2017 Jan;41(1):26-37. doi: 10.1111/acer.13266. Epub 2016 Nov 11.
The consumption of alcohol during pregnancy can result in abnormal fetal development and impaired brain function in humans and experimental animal models. Depending on the pattern of consumption, the dose, and the period of exposure to ethanol (EtOH), a variety of structural and functional brain deficits can be observed.
This study compared the effects of EtOH exposure during distinct periods of brain development on oxidative damage and endogenous antioxidant status in various brain regions of adult female and male Sprague Dawley rats. Pregnant dams and neonatal rats were exposed to EtOH during one of the following time windows: between gestational days (GDs) 1 and 10 (first trimester equivalent); between GDs 11 and 21 (second trimester equivalent); or between postnatal days (PNDs) 4 and 10 (third trimester equivalent).
EtOH exposure during any of the 3 trimester equivalents significantly increased lipid peroxidation in both the cornus ammonis (CA) and dentate gyrus (DG) subregions of the hippocampus, while also decreasing the levels of the endogenous antioxidant glutathione in the hippocampal CA and DG subregions as well as the prefrontal cortex of young adult animals (PND 60).
These results indicate that EtOH exposure during restricted periods of brain development can have long-term consequences in the adult brain by dysregulating its redox status. This dysfunction may underlie, at least in part, the long-term alterations in brain function associated with fetal alcohol spectrum disorders.
孕期饮酒会导致人类和实验动物模型出现胎儿发育异常及脑功能受损。根据饮酒模式、剂量以及乙醇(EtOH)暴露时期的不同,可观察到多种结构和功能上的脑缺陷。
本研究比较了在脑发育的不同时期暴露于EtOH对成年雌性和雄性Sprague Dawley大鼠不同脑区氧化损伤和内源性抗氧化状态的影响。怀孕母鼠和新生大鼠在以下时间窗之一暴露于EtOH:妊娠第1天至第10天(相当于孕早期);妊娠第11天至第21天(相当于孕中期);或出生后第4天至第10天(相当于孕晚期)。
在这3个相当于孕期的任何一个时期暴露于EtOH,均显著增加了海马体的海马角(CA)和齿状回(DG)亚区的脂质过氧化,同时也降低了年轻成年动物(出生后第60天)海马体CA和DG亚区以及前额叶皮质内源性抗氧化剂谷胱甘肽的水平。
这些结果表明,在脑发育的受限时期暴露于EtOH可通过调节其氧化还原状态对成年大脑产生长期影响。这种功能障碍可能至少部分是与胎儿酒精谱系障碍相关的脑功能长期改变的基础。