Methyl Donor-Deficient Diet during Development Can Affect Fear and Anxiety in Adulthood in C57BL/6J Mice

被引:29
|
作者
Ishii, Daisuke [1 ]
Matsuzawa, Daisuke [1 ,2 ]
Matsuda, Shingo [1 ,3 ]
Tomizawa, Haruna [1 ]
Sutoh, Chihiro [1 ,2 ]
Shimizu, Eiji [1 ,2 ]
机构
[1] Chiba Univ, Grad Sch Med, Dept Cognit Behav Physiol, Chiba, Japan
[2] Chiba Univ, Grad Sch Med, Res Ctr Child Mental Dev, Chiba, Japan
[3] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Ultrastruct Res, Tokyo, Japan
来源
PLOS ONE | 2014年 / 9卷 / 08期
基金
日本学术振兴会;
关键词
POSTTRAUMATIC-STRESS-DISORDER; DNA METHYLTRANSFERASES DNMT3A; MONOZYGOTIC TWINS DISCORDANT; NATIONAL COMORBIDITY SURVEY; REGULATES MEMORY FORMATION; EMBRYONIC STEM-CELLS; EPIGENETIC ALTERATIONS; LIFETIME PREVALENCE; UP-REGULATION; GENE;
D O I
10.1371/journal.pone.0105750
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
DNA methylation is one of the essential factors in the control of gene expression. Folic acid, methionine and choline (methyl donors)-all nutrients related to one-carbon metabolism-are known as important mediators of DNA methylation. A previous study has shown that long-term administration of a diet lacking in methyl donors caused global DNA hypermethylation in the brain (Pogribny et al., 2008). However, no study has investigated the effects of a diet lacking in methyl donors during the developmental period on emotional behaviors such as fear and anxiety-like behavior in association with gene expressions in the brain. In addition, it has not been elucidated whether a diet supplemented with methyl donors later in life can reverse these changes. Therefore, we examined the effects of methyl donor deficiency during the developmental period on fear memory acquisition/extinction and anxiety-like behavior, and the relevant gene expressions in the hippocampus in juvenile (6-wk) and adult (12-wk) mice. We found that juvenile mice fed a methyl-donor-deficient diet had impaired fear memory acquisition along with decreases in the gene expressions of Dnmt3a and Dnmt3b. In addition, reduced anxiety-like behavior with decreased gene expressions of Grin2b and Gabar2 was observed in both the methyl-donor-deficient group and the body-weight-matched food-restriction group. After being fed a diet supplemented with methyl donors ad libitum, adult mice reversed the alteration of gene expression of Dnmt3a, Dnmt3b, Grin2b and Gabar2, but anxiety-like behavior became elevated. In addition, impaired fear-memory formation was observed in the adult mice fed the methyl-donor-deficient diet during the developmental period. Our study suggested that developmental alterations in the one-carbon metabolic pathway in the brain could have effects on emotional behavior and memory formation that last into adulthood.
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页数:12
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