{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T16:25:04Z","timestamp":1761841504640},"reference-count":56,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T00:00:00Z","timestamp":1462838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 AA017978"],"award-info":[{"award-number":["RO1 AA017978"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Fetal alcohol spectrum disorder (<jats:styled-content style=\"fixed-case\">FASD<\/jats:styled-content>) is the leading nongenetic cause of mental retardation. There are no treatments for <jats:styled-content style=\"fixed-case\">FASD<\/jats:styled-content> to date. Preclinical in\u00a0vivo and in\u00a0vitro studies could help in identifying novel drug targets as for other diseases. Here, we describe an ex\u00a0vivo model that combines the physiological advantages of prenatal ethanol (EtOH) exposure in\u00a0vivo with the uniformity of primary fetal hippocampal culture to characterize the effects of prenatal EtOH. The insulin signaling pathways are known to be involved in hippocampal functions. Therefore, we compared the expression of insulin signaling pathway genes between fetal hippocampi (in\u00a0vivo) and primary hippocampal culture (ex\u00a0vivo). The similarity of prenatal EtOH effects in these 2 paradigms would deem the ex\u00a0vivo culture acceptable to screen possible treatments for <jats:styled-content style=\"fixed-case\">FASD<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pregnant Sprague\u2013Dawley rats received 1 of 3 diets: ad\u00a0libitum standard laboratory chow (control\u2010C), isocaloric pair\u2010fed (nutritional control), and EtOH containing liquid diets from gestational day (<jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>) 8. Fetal male and female hippocampi were collected either on <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>21 (in\u00a0vivo) or on <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>18 for primary culture (ex\u00a0vivo). Transcript levels of <jats:italic>Igf2<\/jats:italic>,<jats:italic> Igf2r<\/jats:italic>,<jats:italic> Insr<\/jats:italic>,<jats:italic> Grb10<\/jats:italic>,<jats:italic> Rasgrf1<\/jats:italic>, and <jats:italic>Zac1<\/jats:italic> were measured by reverse transcription quantitative polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hippocampal transcript levels differed by prenatal treatment in both males and females with sex differences observed in the expression of <jats:italic>Igf2<\/jats:italic> and <jats:italic>Insr<\/jats:italic>. The effect of prenatal EtOH on the hippocampal expression of the insulin pathway genes was parallel in the in\u00a0vivo and the ex\u00a0vivo conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The similarity of gene expression changes in response to prenatal EtOH between the in\u00a0vivo and the ex\u00a0vivo conditions ascertains that these effects are already set in the fetal hippocampus at <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>18. This strengthens the feasibility of the ex\u00a0vivo primary hippocampal culture as a tool to test and screen candidate drug targets for <jats:styled-content style=\"fixed-case\">FASD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13090","type":"journal-article","created":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T09:59:31Z","timestamp":1462874371000},"page":"1273-1282","source":"Crossref","is-referenced-by-count":9,"title":["Modeling Fetal Alcohol Spectrum Disorder: Validating an Ex Vivo Primary Hippocampal Cell Culture System"],"prefix":"10.1111","volume":"40","author":[{"given":"Elif","family":"Tunc\u2010Ozcan","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences The Asher Center Feinberg School of Medicine Northwestern University Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana B.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Cellular 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