Dietary methyl donor deficiency during pregnancy in rats shapes learning and anxiety in offspring
Dietary methyl donor deficiency during pregnancy in rats shapes learning and anxiety in offspring
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DOI：
10.1016/j.nutres.2011.09.015
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发表时间：
2011-10-01
影响因子：
4.5
通讯作者：
Breier, Bernhard H.
中科院分区：
文献类型：
--
作者：
Konycheva, Galina;Dziadek, Marie A.;Breier, Bernhard H.
两条重要的研究路线加强了我们对营养在影响行为中的分子作用的理解。首先，在生命早期暴露在不利环境中会影响后代的长期行为。其次，神经系统发育和功能的调节似乎涉及表观遗传机制，这需要在食物中持续供应甲基供体。我们推测，孕期缺乏甲基供体(MDD)的母体饮食可能通过海马区DNA甲基化的永久性改变而导致后代的行为改变。我们使用了一种产前饮食MDD的大鼠模型，在雌性后代中验证了这一假设。产前MDD降低了出生体重、产仔数和新生儿存活率。与对照组相比，MDD母亲的老年雌性后代表现出更高的焦虑感和学习能力。为了探讨MDD在成年后代大脑表观遗传机制中的作用，我们研究了糖皮质激素受体、羟基类固醇脱氢酶11型2、神经氨酸和卷曲蛋白4个基因在海马区的表达和甲基化。除了MDD雌性后代中reelin基因的显著下调外，没有发现所研究基因的甲基化或表达方面的主要群体差异。产前MDD饮食导致宫内生长受限，与对后代行为的长期影响有关。然而，观察到的MDD和对照饮食后代之间的行为差异不能用本研究中调查的特定基因的表观遗传调节来解释。(C)2011 Elsevier Inc.保留所有权利。
Two important lines of research have enhanced our understanding of the molecular role of nutrition in influencing behavior. First, exposure to an adverse environment during early life can influence the long-term behavior of the offspring. Second, regulation of the nervous system development and functioning appears to involve epigenetic mechanisms that require a continuous supply of methyl group donors in food. We hypothesized that a maternal diet during pregnancy deficient in methyl donors (MDD) may lead to altered behavior in offspring through permanent changes in hippocampal DNA methylation. We used a rat model of prenatal dietary MDD to test this hypothesis in female offspring as they aged. Prenatal MDD reduced birth weight, litter size, and newborn viability. Aged female offspring of MDD mothers showed increased anxiety and increased learning ability in comparison with control diet group offspring. To explore the role of MDD on epigenetic mechanisms in the brain of adult offspring, we studied expression and methylation of 4 selected genes coding for glucocorticoid receptor, hydroxysteroid dehydrogenase 11 type 2, neuronatin, and reelin proteins in the hippocampus. No major group differences in methylation or expression of the studied genes were detected, except for a significant down-regulation of the reelin gene in the MDD female offspring. The prenatal MDD diet caused intrauterine growth restriction, associated with long-term effects on the behavior of the offspring. However, the observed behavioral differences between the MDD and control diet offspring cannot be explained by epigenetic regulation of the specific genes investigated in this study. (C) 2011 Elsevier Inc. All rights reserved.