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Alteration of the <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation pattern has been linked to various neurological, behavioral and neurocognitive dysfunctions. Recent studies have pointed out the importance of epigenetics in brain development and functions including learning and memory. Nutrients related to one\u2010carbon metabolism are known to play important roles in the maintenance of genomic <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation. Previous studies have shown that the long\u2010term administration of a diet lacking essential one\u2010carbon nutrients such as methionine, choline and folic acid (methyl donors) caused global <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> hypermethylation in the brain. Therefore, the long\u2010term feeding of a methyl\u2010donor\u2010deficient diet may cause abnormal brain development including learning and memory. To confirm this hypothesis, 3\u2010week\u2010old mice were maintained on a folate\u2010, methionine\u2010 and choline\u2010deficient (<jats:styled-content style=\"fixed-case\">FMCD<\/jats:styled-content>) or control (<jats:styled-content style=\"fixed-case\">CON<\/jats:styled-content>) diet for 3 weeks. We found that the methyl\u2010donor deficiency impaired both novel object recognition and fear extinction after 3 weeks of treatment. The <jats:styled-content style=\"fixed-case\">FMCD<\/jats:styled-content> group showed spontaneous recovery of fear that differed from that in <jats:styled-content style=\"fixed-case\">CON<\/jats:styled-content>. In addition, we found decreased <jats:italic>Gria1<\/jats:italic> gene expression and specific <jats:styled-content style=\"fixed-case\">CpG<\/jats:styled-content> hypermethylation of the <jats:italic>Gria1<\/jats:italic> promoter region in the <jats:styled-content style=\"fixed-case\">FMCD<\/jats:styled-content> hippocampus. Our data suggest that a chronic dietary lack of methyl donors in the developmental period affects learning, memory and gene expressions in the hippocampus.<\/jats:p>","DOI":"10.1111\/gbb.12207","type":"journal-article","created":{"date-parts":[[2015,2,19]],"date-time":"2015-02-19T12:35:14Z","timestamp":1424349314000},"page":"301-309","source":"Crossref","is-referenced-by-count":60,"title":["Methyl\u2010donor deficiency in adolescence affects memory and epigenetic status in the mouse hippocampus"],"prefix":"10.1111","volume":"14","author":[{"given":"H.","family":"Tomizawa","sequence":"first","affiliation":[{"name":"Department of Cognitive Behavioral Physiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Matsuzawa","sequence":"additional","affiliation":[{"name":"Department of Cognitive Behavioral Physiology"},{"name":"Research Center for Child Mental Development, Graduate School of Medicine Chiba University  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