Chaudhary Shaista, Sarkar Dipak K
Endocrinology Program, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA.
Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA.
Alcohol Clin Exp Res (Hoboken). 2023 May;47(5):882-892. doi: 10.1111/acer.15061. Epub 2023 Apr 15.
Alcohol drinking during pregnancy often adversely affects brain development among offspring, inducing persistent central nervous system dysfunction. However, it is unknown whether fetal alcohol exposure (FAE) promotes the biochemical characteristics of Alzheimer's disease in offspring.
We used a first- and second-trimester human equivalent rat model of FAE that involves feeding a liquid diet containing 6.7% v/v ethanol from gestational days 7 through 21 in Fischer-344 rats. Control rats were fed an isocaloric liquid diet or rat chow ad libitum. Pups were weaned on postnatal day 21 and housed by sex. They were used for behavioral and biochemical studies at about 12 months of age. Only one male or one female offspring from a litter was included in each experimental group.
Fetal alcohol-exposed offspring had poorer learning and memory functions than controls. The experimental animals, both male and female, also had elevated levels of acetylcholinesterase (AChE) activity, hyperphosphorylated-tau protein, β-amyloid (Aβ) and Aβ1-42 proteins, β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and Unc-5 netrin receptor C (UNC5C) proteins in the cerebral cortex and hippocampus at 12 months of age.
These findings show that FAE increases the expression of some of the biochemical and behavioral phenotypes of Alzheimer's disease.
孕期饮酒通常会对后代的大脑发育产生不利影响，导致持续性中枢神经系统功能障碍。然而，胎儿酒精暴露（FAE）是否会促进后代患阿尔茨海默病的生化特征尚不清楚。
我们使用了一种相当于人类孕早期和孕中期的FAE大鼠模型，该模型是在Fischer-344大鼠妊娠第7天至21天期间，给其喂食含6.7% v/v乙醇的液体饲料。对照大鼠随意喂食等热量的液体饲料或大鼠饲料。幼崽在出生后第21天断奶，并按性别饲养。在大约12个月大时，将它们用于行为和生化研究。每个实验组仅包括一窝中的一只雄性或一只雌性后代。
胎儿酒精暴露的后代的学习和记忆功能比对照组差。在12个月大时，无论是雄性还是雌性实验动物，其大脑皮层和海马体中的乙酰胆碱酯酶（AChE）活性、过度磷酸化的tau蛋白、β-淀粉样蛋白（Aβ）和Aβ1-42蛋白、β-位点淀粉样前体蛋白裂解酶1（BACE1）以及Unc-5神经纤毛蛋白受体C（UNC5C）蛋白水平均升高。
这些发现表明，胎儿酒精暴露会增加阿尔茨海默病的一些生化和行为表型的表达。
