{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:49:43Z","timestamp":1791668983989,"version":"4.3.4"},"reference-count":86,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,4,17]],"date-time":"2012-04-17T00:00:00Z","timestamp":1334620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Some of the most frequent deficits seen in children with fetal alcohol spectrum disorders (<jats:styled-content style=\"fixed-case\">FASD<\/jats:styled-content>) and in animal models of <jats:styled-content style=\"fixed-case\">FASD<\/jats:styled-content> are spatial memory impairments and impaired executive functioning, which are likely related to alcohol\u2010induced alterations of the hippocampus and prefrontal cortex (<jats:styled-content style=\"fixed-case\">PFC<\/jats:styled-content>), respectively. Choline, a nutrient supplement, has been shown in a rat model to ameliorate some of alcohol's teratogenic effects, and this effect may be mediated through choline's effects on <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Alcohol was given by intragastric intubation to rat pups during the neonatal period (postnatal days 2 to 10) (<jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content> group), which is equivalent to the third trimester in humans and a period of heightened vulnerability of the brain to alcohol exposure. Control groups included an intubated control group given the intubation procedure without alcohol (<jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content>) and a nontreated control group (<jats:styled-content style=\"fixed-case\">NC<\/jats:styled-content>). Choline or saline was administered subcutaneously to each subject from postnatal days 2 to 20. On postnatal day 21, the brains of the subjects were removed and assayed for global <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation patterning as measured by chemiluminescence using the cp<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>lobal assay in both the hippocampal region and <jats:styled-content style=\"fixed-case\">PFC<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Alcohol exposure caused hypermethylation in the hippocampus and <jats:styled-content style=\"fixed-case\">PFC<\/jats:styled-content>, which was significantly reduced after choline supplementation. In contrast, control animals showed increases in <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation in both regions after choline supplementation, suggesting that choline supplementation has different effects depending upon the initial state of the brain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study is the first to show changes in global <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation of the hippocampal region and <jats:styled-content style=\"fixed-case\">PFC<\/jats:styled-content> after neonatal alcohol exposure. Choline supplementation impacts global <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation in these 2 brain regions in alcohol\u2010exposed and control animals in a differential manner. The current findings suggest that both alcohol and choline have substantial impact on the epigenome in the <jats:styled-content style=\"fixed-case\">PFC<\/jats:styled-content> and hippocampus, and future studies will be needed to describe which gene families are impacted in such a way that function of the nervous system is changed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1530-0277.2012.01784.x","type":"journal-article","created":{"date-parts":[[2012,4,17]],"date-time":"2012-04-17T15:03:10Z","timestamp":1334674990000},"page":"1701-1709","source":"Crossref","is-referenced-by-count":137,"title":["Choline Supplementation and <scp>DNA<\/scp> Methylation in the Hippocampus and Prefrontal Cortex of Rats Exposed to Alcohol During Development"],"prefix":"10.1111","volume":"36","author":[{"given":"Nicha K. 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