Cantacorps Lídia, Alfonso-Loeches Silvia, Moscoso-Castro Maria, Cuitavi Javier, Gracia-Rubio Irene, López-Arnau Raúl, Escubedo Elena, Guerri Consuelo, Valverde Olga
Neurobiology of Behaviour Research Group (GReNeC-NeuroBio), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
Molecular and Cellular Pathology of Alcohol, Prince Felipe Research Centre, Eduardo Primo Yúfera 3, 46012 Valencia, Spain.
Neuropharmacology. 2017 Sep 1;123:368-384. doi: 10.1016/j.neuropharm.2017.05.034. Epub 2017 Jun 29.
Alcohol binge drinking is on the increase in the young adult population, and consumption during pregnancy can be deleterious for foetal development. Maternal alcohol consumption leads to a wide range of long-lasting morphological and behavioural deficiencies known as foetal alcohol spectrum disorders (FASD), associated with neurodevelopmental disabilities. We sought to test the effects of alcohol on neuroimmune system activation and its potential relation to alcohol-induced neurodevelopmental and persistent neurobehavioural effects in offspring after maternal alcohol binge drinking during the prenatal period or in combination with lactation. Pregnant C57BL/6 female mice underwent a procedure for alcohol binge drinking either during gestation or both the gestation and lactation periods. Adult male offspring were assessed for cognitive functions and motor coordination. Early alcohol exposure induced motor coordination impairments in the rotarod test. Object recognition memory was not affected by maternal alcohol binge drinking, but Y-maze performance was impaired in pre- and early postnatal alcohol-exposed mice. Behavioural effects were associated with an upregulation of pro-inflammatory signalling (Toll-like receptor 4, nuclear factor-kappa B p65, NOD-like receptor protein 3, caspase-1, and interleukin-1β), gliosis, neuronal cell death and a reduction in several structural myelin proteins (myelin-associated glycoprotein, myelin basic protein, myelin proteolipid protein and myelin regulatory factor) in both the prefrontal cortex and hippocampus of adult mice exposed to alcohol. Altogether, our results reveal that maternal binge-like alcohol consumption induces neuroinflammation and myelin damage in the brains of offspring and that such effects may underlie the persistent cognitive and behavioural impairments observed in FASD.
酗酒在年轻成年人群中呈上升趋势，孕期饮酒会对胎儿发育有害。母亲饮酒会导致一系列长期的形态和行为缺陷，即胎儿酒精谱系障碍（FASD），这与神经发育障碍有关。我们试图测试酒精对神经免疫系统激活的影响，以及它与孕期或孕期加哺乳期母亲酗酒后代中酒精诱导的神经发育和持续神经行为影响的潜在关系。怀孕的C57BL/6雌性小鼠在孕期或孕期和哺乳期都接受了酗酒程序。对成年雄性后代进行认知功能和运动协调评估。早期酒精暴露在转棒试验中导致运动协调受损。物体识别记忆不受母亲酗酒的影响，但产前和产后早期酒精暴露的小鼠在Y迷宫测试中的表现受损。行为影响与成年酒精暴露小鼠前额叶皮质和海马中促炎信号（Toll样受体4、核因子-κB p65、NOD样受体蛋白3、半胱天冬酶-1和白细胞介素-1β）的上调、胶质细胞增生、神经元细胞死亡以及几种结构髓磷脂蛋白（髓磷脂相关糖蛋白、髓磷脂碱性蛋白、髓磷脂蛋白脂蛋白和髓磷脂调节因子）的减少有关。总之，我们的结果表明，母亲类似暴饮暴食的酒精消费会导致后代大脑中的神经炎症和髓磷脂损伤，而这些影响可能是FASD中观察到的持续认知和行为障碍的基础。
