Erbas Oytun, Erdogan Mümin Alper, Khalilnezhad Asghar, Gürkan Fulya Tuzcu, Yiğittürk Gürkan, Meral Ayfer, Taskiran Dilek
Istanbul Bilim University School of Medicine, Department of Physiology, Istanbul, Turkey.
Ege University School of Medicine, Department of Physiology, Izmir, Turkey.
Int J Dev Neurosci. 2018 Oct;69:68-79. doi: 10.1016/j.ijdevneu.2018.07.001. Epub 2018 Jul 9.
Previous studies have indicated an association between maternal metabolic conditions and general developmental disturbances of the offspring.
We aimed to investigate the influence of long-term maternal fructose intake during gestation and lactation on neurobehavioral development of rat offspring.
Twelve female Sprague Dawley rats were received either 30% fructose enriched water (n = 6) or regular tap water (control, n = 6) for 12 weeks. Then, control and fructose-received females were caged with a fertile male, and received 30% fructose and regular chow throughout pregnancy, delivery and until offspring's weaning. On P21, forty littermates (10 male control, 10 female control, 10 male fructose and 10 female fructose) were separated and housed with ad libitum access to standard food and tap water. Following behavioral evaluations at P50, brain levels of TNF-α, neuregulin 1 (NRG1), glutamic acid decarboxylase 67 (GAD67), nerve growth factor (NGF), insulin-like growth factor 1 (IGF-1), and 5-hydroxyindoleacetic acid (5-HIAA) were measured. Histologically, hippocampal neuronal density and GFAP expression were assessed.
Analysis of the behavioral tests (three-chamber social test, open field test, passive avoidance learning test and stereotypy test) revealed significant differences among the groups. Histologically, hippocampal CA1 and CA3 regions displayed significant alterations such as gliosis and neuronal cell death in fructose-exposed groups compare to controls. Biochemical measurements of the brain levels of TNF-α and neurodevelopmental markers showed significant differences between controls and fructose-exposed groups.
These results suggest a possible link between the chronic maternal metabolic stress, such as long-term fructose intake, and neurodevelopmental disturbances in the offspring.
先前的研究表明，母亲的代谢状况与后代的一般发育障碍之间存在关联。
我们旨在研究孕期和哺乳期母亲长期摄入果糖对大鼠后代神经行为发育的影响。
12只雌性斯普拉格-道利大鼠接受30%果糖富集水（n = 6）或普通自来水（对照组，n = 6），持续12周。然后，将对照组和摄入果糖的雌性大鼠与一只可育雄性大鼠关在一起，并在整个孕期、分娩期直至后代断奶期间给予30%果糖和常规食物。在出生后第21天（P21），将40只同窝幼崽（10只雄性对照组、10只雌性对照组、10只雄性果糖组和10只雌性果糖组）分开饲养，自由获取标准食物和自来水。在P50进行行为评估后，测量大脑中肿瘤坏死因子-α（TNF-α）、神经调节蛋白1（NRG1）、谷氨酸脱羧酶67（GAD67）、神经生长因子（NGF）、胰岛素样生长因子1（IGF-1）和5-羟色胺酸（5-HIAA）的水平。组织学上，评估海马神经元密度和胶质纤维酸性蛋白（GFAP）表达。
行为测试（三室社交测试、旷场测试、被动回避学习测试和刻板行为测试）分析显示各组之间存在显著差异。组织学上，与对照组相比，暴露于果糖的组中海马CA1和CA3区域显示出明显的改变，如胶质增生和神经元细胞死亡。大脑中TNF-α水平和神经发育标志物的生化测量显示对照组和暴露于果糖的组之间存在显著差异。
这些结果表明，长期果糖摄入等慢性母体代谢应激与后代神经发育障碍之间可能存在联系。
