Prenatal ethanol exposure induces an intrauterine programming of enhanced sensitivity of the hypothalamic-pituitary-adrenal axis in female offspring rats fed with post-weaning high-fat diet
Prenatal ethanol exposure induces an intrauterine programming of enhanced sensitivity of the hypothalamic-pituitary-adrenal axis in female offspring rats fed with post-weaning high-fat diet
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产前乙醇暴露可诱导断奶后高脂饮食喂养的雌性子代大鼠下丘脑-垂体-肾上腺轴敏感性增强的宫内编程
DOI：
10.1039/c5tx00012b
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发表时间：
2015-01-01
影响因子：
2.1
通讯作者：
Wang, Hui
中科院分区：
文献类型：
--
作者：
Lu, Juan;Wen, Yinxian;Wang, Hui
我们以前的研究表明，产前乙醇暴露（PEE）增强下丘脑-垂体-肾上腺（HPA）轴的敏感性在成年后代大鼠。本研究旨在探讨其潜在的机制。PEE处理的雌性子代大鼠用高脂饲料喂养，并在成年后经受不可预测的慢性应激（UCS）。对于成年后代，PEE组表现出下丘脑促肾上腺皮质激素释放激素（CRH）和精氨酸加压素（AVP）的表达增加，以及血清促肾上腺皮质激素（ACTH）和皮质酮的增加率后UCS。同时，PEE显著降低了成年PEE仔鼠谷氨酸脱羧酶65（GAD 65）和Reelin（Reln）的表达，提高了下丘脑囊泡谷氨酸转运体2（VGluT 2）/GAD 65的表达比例。海马组织糖皮质激素受体（GR）、N-甲基-D-天冬氨酸谷氨酸受体2B亚型表达增强，盐皮质激素受体（MR）/GR表达比值降低。海马神经元异常，以CA 3和齿状回亚区为多。对于胎儿，PEE显著降低哺乳动物无毛鳞片同源物1（Mash 1）以及GAD 65和Reln的表达。PEE组VGluT 2/GAD 65表达比值和GR表达均升高，MR/GR表达比值降低。PEE还引起CA 3区超微结构损伤。我们的研究结果表明，PEE导致海马结构的持续重塑改变受损的形态和MR/GR表达的比例下降，以及不平衡的下丘脑的多巴胺能/GABA能传入输入。所有这些都将有助于增强HPA轴在成年后代的敏感性。
Our previous study demonstrated that prenatal ethanol exposure (PEE) enhances the sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis in adult offspring rats. This study aims to investigate the underlying mechanism. PEE treated female offspring rats were fed with high-fat diet and subjected to the unpredictable chronic stresses (UCS) in adulthood. For adult offspring, the PEE group exhibited increased expression of hypothalamic corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) as well as elevated gain rates of serum adrenocorticotropic hormone (ACTH) and corticosterone after UCS. Meanwhile, PEE significantly decreased the expression of glutamic acid decarboxylase 65 (GAD65) and Reelin (Reln), and the expression ratio of hypothalamic vesicular glutamate transporter 2 (VGluT2)/GAD65 was enhanced in the adult PEE offspring. These changes were also accompanied by the enhanced expression of glucocorticoid receptor (GR), N-methyl-D-aspartate-subtype glutamate receptor 2B and the decreased expression ratio of mineralocorticoid receptor (MR)/GR in the hippocampus. Furthermore, the abnormal hippocampus neurons were observed especially in the cornu ammonis 3 (CA3) and dentate gyrus subfields. For fetuses, PEE significantly decreased the expression of mammalian achaete-scute homolog-1 (Mash1) as well as GAD65 and Reln. Both VGluT2/GAD65 expression ratio and GR expression were increased while the MR/GR expression ratio was decreased in the PEE group. PEE also caused ultrastructural injury in CA3. Our findings suggest that PEE causes the persistent remodeling alterations of impaired morphology and decreased MR/GR expression ratio in the hippocampus, as well as the imbalanced glutamatergic/GABAergic afferent inputs in the hypothalamus. All of these would contribute to the enhanced sensitivity of the HPA axis in adult offspring.