論文

査読有り
2014年8月

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

PLOS ONE
  • Daisuke Ishii
  • ,
  • Daisuke Matsuzawa
  • ,
  • Shingo Matsuda
  • ,
  • Haruna Tomizawa
  • ,
  • Chihiro Sutoh
  • ,
  • Eiji Shimizu

9
8
開始ページ
e105750
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0105750
出版者・発行元
PUBLIC LIBRARY SCIENCE

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.

Web of Science ® 被引用回数 : 22

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0105750
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25144567
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000341106100116&DestApp=WOS_CPL
ID情報
  • DOI : 10.1371/journal.pone.0105750
  • ISSN : 1932-6203
  • PubMed ID : 25144567
  • Web of Science ID : WOS:000341106100116

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