{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T22:47:09Z","timestamp":1778885229693,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,2,8]],"date-time":"2018-02-08T00:00:00Z","timestamp":1518048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000360","name":"Scottish Funding Council","doi-asserted-by":"publisher","award":["SCD\/09"],"award-info":[{"award-number":["SCD\/09"]}],"id":[{"id":"10.13039\/501100000360","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Preterm birth affects 5\u201318% of all babies and is associated with neurodevelopmental impairment and increased neuropsychiatric disease risk. Although preterm birth associates with differential <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation at neurodevelopmental genes in buccal <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>, including leucine\u2010rich alpha\u20102\u2010glycoprotein 1 (<jats:styled-content style=\"fixed-case\">LRG<\/jats:styled-content>1), it is not known whether these differences also occur in the brain, or whether they persist. Thus, there is a need for animal models or <jats:italic>in\u00a0vitro<\/jats:italic> systems in which to undertake longitudinal and mechanistic studies. We used a combination of <jats:italic>in\u00a0vivo<\/jats:italic> rat studies and <jats:italic>ex\u00a0vivo<\/jats:italic> experiments in rat cortical slices to explore their utility in modelling the human preterm brain. We identified temporal changes in <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation at <jats:styled-content style=\"fixed-case\">LRG<\/jats:styled-content>1 in human buccal <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> over the first year of life and found persistent differences in <jats:styled-content style=\"fixed-case\">LRG<\/jats:styled-content>1 methylation between preterm and term infants at 1\u00a0year. These developmental changes also occurred in rat brains <jats:italic>in\u00a0vivo<\/jats:italic>, alongside changes in global <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> hydroxymethylation and expression of the ten\u2010eleven translocation (Tet1) enzyme, and were reproducible in <jats:italic>ex\u00a0vivo<\/jats:italic> rat cortical slices. On the basis of the observation that neonatal glucose homeostasis can modify neurodevelopmental outcome, we studied whether glucose concentration affects Lrg1 methylation using cortical slices. Culture of slices in lower glucose concentration was associated with lower Lrg1 methylation, lower global 5hmC and Tet1 expression. Our results suggest that <jats:italic>ex\u00a0vivo<\/jats:italic> organotypic cultures may be useful in the study of biological and environmental influences on the epigenome and that perturbations during early life including glucose concentration can affect methylation at specific genes implicated in neurodevelopment.<\/jats:p>","DOI":"10.1111\/ejn.13825","type":"journal-article","created":{"date-parts":[[2018,1,22]],"date-time":"2018-01-22T16:48:32Z","timestamp":1516639712000},"page":"380-387","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Alterations in glucose concentrations affect <scp>DNA<\/scp> methylation at <i>Lrg1<\/i> in an <i>ex\u00a0vivo<\/i> rat cortical slice model of preterm brain injury"],"prefix":"10.1111","volume":"47","author":[{"given":"Jessy","family":"Cartier","sequence":"first","affiliation":[{"name":"The Queen's Medical Research Institute University\/British Heart Foundation Centre for Cardiovascular Science University of Edinburgh 47 Little France Crescent Edinburgh EH16 4TJ UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chinthika","family":"Piyasena","sequence":"additional","affiliation":[{"name":"The Queen's Medical Research Institute University\/British Heart Foundation Centre for Cardiovascular Science University of Edinburgh 47 Little France Crescent Edinburgh EH16 4TJ UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah A.","family":"Sparrow","sequence":"additional","affiliation":[{"name":"MRC Centre for Reproductive Health The Queen's Medical Research Institute University of Edinburgh Edinburgh UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P.","family":"Boardman","sequence":"additional","affiliation":[{"name":"MRC Centre for Reproductive Health The Queen's Medical Research Institute University of Edinburgh Edinburgh UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8633-333X","authenticated-orcid":false,"given":"Amanda J.","family":"Drake","sequence":"additional","affiliation":[{"name":"The Queen's Medical Research Institute University\/British Heart Foundation Centre for Cardiovascular Science University of Edinburgh 47 Little France Crescent Edinburgh EH16 4TJ UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,2,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8417-2-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2014-306742"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2013.204"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2005-1919"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-2822"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.039099"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22489"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.13"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15132"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2016-310936"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e318212faa0"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2014-307684"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2014.94"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1217750110"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0074453"},{"key":"e_1_2_9_17_1","first-page":"97","article-title":"Brain localization of leucine\u2010rich alpha2\u2010glycoprotein and its role","volume":"113","author":"Nakajima M.","year":"2012","journal-title":"Act. 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