Methyl Donor-Deficient Diet during Development Can Affect Fear and Anxiety in Adulthood in C57BL-6J MiceReport as inadecuate




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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.



Author: Daisuke Ishii , Daisuke Matsuzawa, Shingo Matsuda, Haruna Tomizawa, Chihiro Sutoh, Eiji Shimizu

Source: http://plos.srce.hr/



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