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母体慢性叶酸补充通过改变子代海马脑源性神经营养因子和谷氨酸受体 2B 的甲基化改善产前高脂饮食诱导的行为障碍。

Maternal Chronic Folate Supplementation Ameliorates Behavior Disorders Induced by Prenatal High-Fat Diet Through Methylation Alteration of BDNF and Grin2b in Offspring Hippocampus.

机构信息

Department of Medicine, Columbia University, New York, NY, USA.

Department of Biochemistry and Molecular Biology, Binzhou Medical College, Yantai, Shandong, China.

出版信息

Mol Nutr Food Res. 2017 Dec;61(12). doi: 10.1002/mnfr.201700461. Epub 2017 Oct 26.

Abstract

SCOPE

Maternal consumption of a high-fat diet (HFD) during pregnancy increases the risk of behavioral problems. Folate plays an important role in neuroplasticity and the preservation of neuronal integrity. This study aims at determining the influence of diets supplemented with folate on offspring behavior, and the mechanisms involved.

METHODS AND RESULTS

Female mice were fed a control diet, an HFD, control diet supplemented with folate, or an HFD supplemented with folate for 5 weeks before mating. Open field task and elevated plus maze are used to evaluate the offspring behaviors. Results showed that offspring cognitive performance and anxiety-related behaviors, including those related to open field exploration and elevated plus maze, were significantly improved when dams were treated with folate in pregnancy. Moreover, the maternal folate supplement decreased BDNF and Grin2b methylation and upregulated their expressions in the brain of offspring, which were associated with decreasing the expression of DNA methyltransferases compared with those dams were treated only HFD in pregnancy.

CONCLUSION

Maternal folate supplementation ameliorates behavior disorders induced by prenatal high-fat diet. The beneficial effects were associated with methylation and expression alteration of BDNF and Grin2b genes.

摘要

范围

孕期高脂肪饮食(HFD)的摄入会增加行为问题的风险。叶酸在神经可塑性和神经元完整性的保护中起着重要作用。本研究旨在确定补充叶酸的饮食对后代行为的影响及其相关机制。

方法和结果

在交配前,雌性小鼠被喂食对照饮食、HFD、叶酸补充对照饮食或叶酸补充 HFD 5 周。使用旷场任务和高架十字迷宫来评估后代的行为。结果表明,当母亲在孕期接受叶酸治疗时,后代的认知表现和焦虑相关行为(包括与旷场探索和高架十字迷宫相关的行为)得到显著改善。此外,母体叶酸补充降低了 BDNF 和 Grin2b 的甲基化,并上调了它们在后代大脑中的表达,与仅在孕期接受 HFD 治疗的母体相比,这与 DNA 甲基转移酶的表达降低有关。

结论

母体叶酸补充可改善产前高脂肪饮食引起的行为障碍。这种有益的作用与 BDNF 和 Grin2b 基因的甲基化和表达改变有关。

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