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Mammalian target of rapamycin (mTOR) plays a key role in regulating protein synthesis in response to neuronal activity, thereby modulating synaptic plasticity and long\u2010term memory formation in the brain. Based on our previous quantitative mass spectrometry proteomic studies, we hypothesized that gestational chronic binge alcohol exposure alters mTOR signaling and downstream pathways in the fetal hippocampus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pregnant Sprague\u2010Dawley rats were assigned to either a pair\u2010fed control (PF\u2010Cont) or a binge alcohol (Alcohol) treatment group. Alcohol dams were acclimatized via a once\u2010daily orogastric gavage of 4.5\u00a0g\/kg alcohol (peak BAC, 216\u00a0mg\/dl) from GD 5\u201310 and progressed to 6\u00a0g\/kg alcohol (peak BAC, 289\u00a0mg\/dl) from GD 11\u201321. Pair\u2010fed dams similarly received isocaloric maltose dextrin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the Alcohol group, following this exposure paradigm, fetal body weight and crown\u2010rump length were decreased. The phosphorylation level of mTOR (P\u2010mTOR) in the fetal hippocampus was decreased in the Alcohol group compared with controls. Alcohol exposure resulted in dysregulation of fetal hippocampal mTORC1 signaling, as evidenced by an increase in total 4E\u2010BP1 expression. Phosphorylation levels of 4E\u2010BP1 and p70 S6K were also increased following alcohol exposure. P\u2010mTOR and P\u20104E\u2010BP1 were exclusively detected in the dentate gyrus and oriens layer of the fetal hippocampus, respectively. DEPTOR and RICTOR expression levels in the fetal hippocampus were increased; however, RAPTOR was not altered by chronic binge alcohol exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We conclude that chronic binge alcohol exposure during pregnancy alters mTORC1 signaling pathway in the fetal hippocampus. We conjecture that this dysregulation of mTOR protein expression, its activity, and downstream proteins may play a critical role in FASD neurobiological phenotypes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14348","type":"journal-article","created":{"date-parts":[[2020,4,25]],"date-time":"2020-04-25T17:39:57Z","timestamp":1587836397000},"page":"1329-1336","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Chronic Binge Alcohol Exposure During Pregnancy Alters mTOR System in Rat Fetal Hippocampus"],"prefix":"10.1111","volume":"44","author":[{"given":"Jehoon","family":"Lee","sequence":"first","affiliation":[{"name":"From the Department of Veterinary Physiology and Pharmacology College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University College Station Texas 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