{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:49:24Z","timestamp":1791668964875,"version":"4.3.4"},"reference-count":103,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R37AA012446"],"award-info":[{"award-number":["R37AA012446"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01AA022460"],"award-info":[{"award-number":["R01AA022460"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["T32AA007456-38"],"award-info":[{"award-number":["T32AA007456-38"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["T32AA013525-21"],"award-info":[{"award-number":["T32AA013525-21"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alcohol (ethanol) exposure during pregnancy can adversely affect development, with long-lasting consequences that include neuroimmune, cognitive, and behavioral dysfunction. Alcohol-induced alterations in cytokine levels in the hippocampus may contribute to abnormal cognitive and behavioral outcomes in individuals with fetal alcohol spectrum disorders (FASD). Nutritional intervention with the essential nutrient choline can improve hippocampal-dependent behavioral impairments and may also influence neuroimmune function. Thus, we examined the effects of choline supplementation on hippocampal cytokine levels in adolescent and adult rats exposed to alcohol early in development. From postnatal day (PD) 4\u20139 (third trimester-equivalent), Sprague\u2013Dawley rat pups received ethanol (5.25 g\/kg\/day) or sham intubations and were treated with choline chloride (100 mg\/kg\/day) or saline from PD 10\u201330; hippocampi were collected at PD 35 or PD 60. Age-specific ethanol-induced increases in interferon gamma (IFN-\u03b3), tumor necrosis factor alpha (TNF-\u03b1), and keratinocyte chemoattractant\/human growth-regulated oncogene (KC\/GRO) were identified in adulthood, but not adolescence, whereas persistent ethanol-induced increases of interleukin-6 (IL-6) levels were present at both ages. Interestingly, choline supplementation reduced age-related changes in interleukin-1 beta (IL-1\u03b2) and interleukin-5 (IL-5) as well as mitigating the long-lasting increase in IFN-\u03b3 in ethanol-exposed adults. Moreover, choline influenced inflammatory tone by modulating ratios of pro- to -anti-inflammatory cytokines. These results suggest that ethanol-induced changes in hippocampal cytokine levels are more evident during adulthood than adolescence, and that choline can mitigate some effects of ethanol exposure on long-lasting inflammatory tone.<\/jats:p>","DOI":"10.3390\/cells12040546","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T04:21:59Z","timestamp":1675830119000},"page":"546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Choline Supplementation Alters Hippocampal Cytokine Levels in Adolescence and Adulthood in an Animal Model of Fetal Alcohol Spectrum Disorders"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4527-0640","authenticated-orcid":false,"given":"Jessica A.","family":"Baker","sequence":"first","affiliation":[{"name":"Center for Behavioral Teratology, San Diego State University, San Diego, CA 92120, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7301-5700","authenticated-orcid":false,"given":"Tamara S.","family":"Bodnar","sequence":"additional","affiliation":[{"name":"Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9996-9134","authenticated-orcid":false,"given":"Kristen R.","family":"Breit","sequence":"additional","affiliation":[{"name":"Center for Behavioral Teratology, San Diego State University, San Diego, CA 92120, USA"},{"name":"Department of Psychology, West Chester University, West Chester, PA 19383, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7937-3904","authenticated-orcid":false,"given":"Joanne","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer D.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Center for Behavioral Teratology, San Diego State University, San Diego, CA 92120, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"365","DOI":"10.15585\/mmwr.mm6816a1","article-title":"Consumption of Alcohol Beverages and Binge Drinking among Pregnant Women Aged 18-44 Years\u2014United States, 2015\u20132017","volume":"68","author":"Denny","year":"2019","journal-title":"MMWR Morb. Mortal Wkly. Rep."},{"key":"ref_2","first-page":"529","article-title":"Alcohol use among pregnant and nonpregnant women of childbearing age\u2014United States, 1991-2005","volume":"58","author":"Denny","year":"2009","journal-title":"MMWR Morb. Mortal Wkly. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11065-011-9166-x","article-title":"Fetal alcohol spectrum disorders: An overview","volume":"21","author":"Riley","year":"2011","journal-title":"Neuropsychol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"108918","DOI":"10.1016\/j.drugalcdep.2021.108918","article-title":"Estimating the community prevalence, child traits, and maternal risk factors of fetal alcohol spectrum disorders (FASD) from a random sample of school children","volume":"227","author":"May","year":"2021","journal-title":"Drug Alcohol Depend."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1001\/jama.2017.21896","article-title":"Prevalence of Fetal Alcohol Spectrum Disorders in 4 US Communities","volume":"319","author":"May","year":"2018","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/acer.12939","article-title":"Worldwide Prevalence of Fetal Alcohol Spectrum Disorders: A Systematic Literature Review Including Meta-Analysis","volume":"40","author":"Roozen","year":"2016","journal-title":"Alcohol Clin. Exp. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s10578-015-0566-7","article-title":"Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE): Proposed DSM-5 Diagnosis","volume":"47","author":"Kable","year":"2016","journal-title":"Child Psychiatry Hum. Dev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1002\/jnr.24735","article-title":"Neuroinflammatory contribution of microglia and astrocytes in fetal alcohol spectrum disorders","volume":"99","author":"Kane","year":"2021","journal-title":"J. Neurosci. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1002\/dneu.22035","article-title":"Neuroimmune mechanisms in fetal alcohol spectrum disorder","volume":"72","author":"Kane","year":"2012","journal-title":"Dev. Neurobiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.neubiorev.2016.05.035","article-title":"Immunoadolescence: Neuroimmune development and adolescent behavior","volume":"70","author":"Brenhouse","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.bbi.2010.08.003","article-title":"Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome","volume":"25","author":"Ashwood","year":"2011","journal-title":"Brain Behav. Immun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/mp.2016.77","article-title":"Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation","volume":"22","author":"Jones","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1586\/14737175.7.7.797","article-title":"Prenatal infectious and nutritional factors and risk of adult schizophrenia","volume":"7","author":"Penner","year":"2007","journal-title":"Expert Rev. Neurother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1111\/j.1530-0277.2006.00084.x","article-title":"Cytokines and alcohol","volume":"30","author":"Crews","year":"2006","journal-title":"Alcohol Clin. Exp. Res."},{"key":"ref_15","first-page":"167","article-title":"Adolescent neuroimmune function and its interaction with alcohol","volume":"161","author":"Deak","year":"2022","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0741-8329(00)00076-8","article-title":"Alcohol modulates cytokine secretion and synthesis in human fetus: An in vivo and in vitro study","volume":"21","author":"Ahluwalia","year":"2000","journal-title":"Alcohol"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.alcohol.2017.08.006","article-title":"Implications of altered maternal cytokine concentrations on infant outcomes in children with prenatal alcohol exposure","volume":"68","author":"Sowell","year":"2018","journal-title":"Alcohol"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.bbi.2018.05.004","article-title":"Altered maternal immune networks are associated with adverse child neurodevelopment: Impact of alcohol consumption during pregnancy","volume":"73","author":"Bodnar","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12974-020-1717-8","article-title":"Immune network dysregulation associated with child neurodevelopmental delay: Modulatory role of prenatal alcohol exposure","volume":"17","author":"Bodnar","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.bbi.2016.05.022","article-title":"Evidence for an immune signature of prenatal alcohol exposure in female rats","volume":"58","author":"Bodnar","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1111\/acer.12639","article-title":"Pioglitazone blocks ethanol induction of microglial activation and immune responses in the hippocampus, cerebellum, and cerebral cortex in a mouse model of fetal alcohol spectrum disorders","volume":"39","author":"Drew","year":"2015","journal-title":"Alcohol Clin. Exp. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.neuroscience.2016.03.033","article-title":"Neonatal binge alcohol exposure increases microglial activation in the developing rat hippocampus","volume":"324","author":"Boschen","year":"2016","journal-title":"Neuroscience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s11481-017-9774-1","article-title":"Sex Differences in Early Postnatal Microglial Colonization of the Developing Rat Hippocampus Following a Single-Day Alcohol Exposure","volume":"13","author":"Ruggiero","year":"2018","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1002\/glia.22835","article-title":"Transient activation of microglia following acute alcohol exposure in developing mouse neocortex is primarily driven by BAX-dependent neurodegeneration","volume":"63","author":"Ahlers","year":"2015","journal-title":"Glia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s12974-015-0382-9","article-title":"Exposure of neonatal rats to alcohol has differential effects on neuroinflammation and neuronal survival in the cerebellum and hippocampus","volume":"12","author":"Topper","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1007\/s11481-016-9691-8","article-title":"Effects of Moderate Prenatal Alcohol Exposure during Early Gestation in Rats on Inflammation across the Maternal-Fetal-Immune Interface and Later-Life Immune Function in the Offspring","volume":"11","author":"Terasaki","year":"2016","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1038\/s41386-019-0326-7","article-title":"Early life alcohol exposure primes hypothalamic microglia to later-life hypersensitivity to immune stress: Possible epigenetic mechanism","volume":"44","author":"Chastain","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.neuropharm.2017.05.034","article-title":"Maternal alcohol binge drinking induces persistent neuroinflammation associated with myelin damage and behavioural dysfunctions in offspring mice","volume":"123","author":"Cantacorps","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Terasaki, L.S., and Schwarz, J.M. (2017). Impact of Prenatal and Subsequent Adult Alcohol Exposure on Pro-Inflammatory Cytokine Expression in Brain Regions Necessary for Simple Recognition Memory. Brain Sci., 7.","DOI":"10.3390\/brainsci7100125"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"155126","DOI":"10.1016\/j.cyto.2020.155126","article-title":"Gene expression profiling reveals a lingering effect of prenatal alcohol exposure on inflammatory-related genes during adolescence and adulthood","volume":"133","author":"Gano","year":"2020","journal-title":"Cytokine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3389\/fnbeh.2020.00082","article-title":"Lingering Effects of Prenatal Alcohol Exposure on Basal and Ethanol-Evoked Expression of Inflammatory-Related Genes in the CNS of Adolescent and Adult Rats","volume":"14","author":"Youngentob","year":"2020","journal-title":"Front. Behav. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"621S","DOI":"10.1080\/07315724.2004.10719433","article-title":"Nutritional importance of choline for brain development","volume":"23","author":"Zeisel","year":"2004","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/j.1753-4887.2006.tb00202.x","article-title":"Perinatal choline influences brain structure and function","volume":"64","author":"Zeisel","year":"2006","journal-title":"Nutr. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.neubiorev.2005.12.003","article-title":"An overview of evidence for a causal relationship between dietary availability of choline during development and cognitive function in offspring","volume":"30","author":"McCann","year":"2006","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"528S","DOI":"10.1080\/07315724.2000.10718976","article-title":"Choline: Needed for normal development of memory","volume":"19","author":"Zeisel","year":"2000","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ntt.2016.11.007","article-title":"Dietary choline levels modify the effects of prenatal alcohol exposure in rats","volume":"59","author":"Idrus","year":"2017","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.brainres.2008.08.048","article-title":"Choline supplementation attenuates learning deficits associated with neonatal alcohol exposure in the rat: Effects of varying the timing of choline administration","volume":"1237","author":"Ryan","year":"2008","journal-title":"Brain Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1037\/0735-7044.121.1.120","article-title":"Choline supplementation following third-trimester-equivalent alcohol exposure attenuates behavioral alterations in rats","volume":"121","author":"Thomas","year":"2007","journal-title":"Behav. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.ntt.2009.07.002","article-title":"Prenatal choline supplementation mitigates the adverse effects of prenatal alcohol exposure on development in rats","volume":"31","author":"Thomas","year":"2009","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1002\/bdra.20713","article-title":"Prenatal choline supplementation mitigates behavioral alterations associated with prenatal alcohol exposure in rats","volume":"88","author":"Thomas","year":"2010","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Grafe, E.L., Wade, M.M.M., Hodson, C.E., Thomas, J.D., and Christie, B.R. (2022). Postnatal Choline Supplementation Rescues Deficits in Synaptic Plasticity Following Prenatal Ethanol Exposure. Nutrients, 14.","DOI":"10.3390\/nu14102004"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1002\/hipo.20925","article-title":"Choline supplementation mitigates trace, but not delay, eyeblink conditioning deficits in rats exposed to alcohol during development","volume":"22","author":"Thomas","year":"2012","journal-title":"Hippocampus"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S0892-0362(00)00097-0","article-title":"Neonatal choline supplementation ameliorates the effects of prenatal alcohol exposure on a discrimination learning task in rats","volume":"22","author":"Thomas","year":"2000","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1111\/acer.14672","article-title":"Maternal choline supplementation mitigates alcohol exposure effects on neonatal brain volumes","volume":"45","author":"Warton","year":"2021","journal-title":"Alcohol Clin. Exp. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1111\/acer.13769","article-title":"Efficacy of Maternal Choline Supplementation during Pregnancy in Mitigating Adverse Effects of Prenatal Alcohol Exposure on Growth and Cognitive Function: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial","volume":"42","author":"Jacobson","year":"2018","journal-title":"Alcohol Clin. Exp. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s11689-020-09312-7","article-title":"Four-year follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder","volume":"12","author":"Wozniak","year":"2020","journal-title":"J. Neurodev. Disord."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Derbyshire, E., and Obeid, R. (2020). Choline, Neurological Development and Brain Function: A Systematic Review Focusing on the First 1000 Days. Nutrients, 12.","DOI":"10.3390\/nu12061731"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.bbi.2005.03.015","article-title":"The cholinergic anti-inflammatory pathway","volume":"19","author":"Pavlov","year":"2005","journal-title":"Brain Behav. Immun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.3389\/fimmu.2017.01489","article-title":"The Cholinergic System Modulates Memory and Hippocampal Plasticity via Its Interactions with Non-Neuronal Cells","volume":"8","author":"Maurer","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.bbi.2015.02.005","article-title":"The interaction between maternal immune activation and alpha 7 nicotinic acetylcholine receptor in regulating behaviors in the offspring","volume":"46","author":"Wu","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.bcp.2015.07.032","article-title":"Anti-inflammatory role of microglial alpha7 nAChRs and its role in neuroprotection","volume":"97","author":"Egea","year":"2015","journal-title":"Biochem. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1089\/ars.2012.4671","article-title":"The microglial alpha7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2","volume":"19","author":"Parada","year":"2013","journal-title":"Antioxid. Redox Signal"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1002\/ana.22664","article-title":"Resolving postoperative neuroinflammation and cognitive decline","volume":"70","author":"Terrando","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_54","first-page":"600","article-title":"Choline improves lipopolysaccharide-induced central nervous system inflammatory response and cognitive dysfunction in mice","volume":"37","author":"Yu","year":"2017","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1002\/jcp.24526","article-title":"Choline inadequacy impairs trophoblast function and vascularization in cultured human placental trophoblasts","volume":"229","author":"Jiang","year":"2014","journal-title":"J. Cell Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.placenta.2017.03.019","article-title":"Maternal choline supplementation during murine pregnancy modulates placental markers of inflammation, apoptosis and vascularization in a fetal sex-dependent manner","volume":"53","author":"Kwan","year":"2017","journal-title":"Placenta"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1177\/1933719117702247","article-title":"Choline Supplementation During Pregnancy Protects Against Gestational Lipopolysaccharide-Induced Inflammatory Responses","volume":"25","author":"Zhang","year":"2018","journal-title":"Reprod. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Baker, J.A., Breit, K.R., Bodnar, T.S., Weinberg, J., and Thomas, J.D. (2022). Choline Supplementation Modifies the Effects of Developmental Alcohol Exposure on Immune Responses in Adult Rats. Nutrients, 14.","DOI":"10.3390\/nu14142868"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7368","DOI":"10.1523\/JNEUROSCI.5746-12.2013","article-title":"Modeling transformations of neurodevelopmental sequences across mammalian species","volume":"33","author":"Workman","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ntt.2003.10.002","article-title":"Perinatal choline supplementation attenuates behavioral alterations associated with neonatal alcohol exposure in rats","volume":"26","author":"Thomas","year":"2004","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0892-0362(97)00062-7","article-title":"Neonatal binge ethanol exposure using intubation: Timing and dose effects on place learning","volume":"19","author":"Goodlett","year":"1997","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.1530-0277.1987.tb01308.x","article-title":"Developmental changes in alcohol pharmacokinetics in rats","volume":"11","author":"Kelly","year":"1987","journal-title":"Alcohol Clin. Exp. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/978-1-59745-242-7_8","article-title":"Intragastric intubation of alcohol during the perinatal period","volume":"447","author":"Kelly","year":"2008","journal-title":"Methods Mol. Biol."},{"key":"ref_64","first-page":"54947","article-title":"Wheel Running and Environmental Complexity as a Therapeutic Intervention in an Animal Model of FASD","volume":"120","author":"Gursky","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.brainresrev.2010.04.011","article-title":"Hippocampal cell loss and neurogenesis after fetal alcohol exposure: Insights from different rodent models","volume":"64","author":"Boehme","year":"2010","journal-title":"Brain Res. Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.alcohol.2015.12.002","article-title":"The impact of prenatal alcohol exposure on social, cognitive and affective behavioral domains: Insights from rodent models","volume":"51","author":"Marquardt","year":"2016","journal-title":"Alcohol"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3389\/fped.2014.00093","article-title":"A comparison of the different animal models of fetal alcohol spectrum disorders and their use in studying complex behaviors","volume":"2","author":"Patten","year":"2014","journal-title":"Front. Pediatr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3109\/10408363.2011.580567","article-title":"Molecular and behavioral aspects of the actions of alcohol on the adult and developing brain","volume":"48","author":"Guerri","year":"2011","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1002\/dneu.22448","article-title":"Impact of exercise and a complex environment on hippocampal dendritic morphology, Bdnf gene expression, and DNA methylation in male rat pups neonatally exposed to alcohol","volume":"77","author":"Boschen","year":"2017","journal-title":"Dev. Neurobiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/j.1369-1600.2009.00192.x","article-title":"Ethanol consumption: How should we measure it? Achieving consilience between human and animal phenotypes","volume":"15","author":"Leeman","year":"2010","journal-title":"Addict. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0166-4328(00)00263-1","article-title":"Critical periods for the effects of alcohol exposure on brain weight, body weight, activity and investigation","volume":"116","author":"Tran","year":"2000","journal-title":"Behav. Brain Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1002\/hipo.22009","article-title":"The effects of perinatal choline supplementation on hippocampal cholinergic development in rats exposed to alcohol during the brain growth spurt","volume":"22","author":"Monk","year":"2012","journal-title":"Hippocampus"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.alcohol.2016.12.006","article-title":"Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure","volume":"60","author":"Balaraman","year":"2017","journal-title":"Alcohol"},{"key":"ref_74","first-page":"624","article-title":"The Laboratory Rat: Relating Its Age With Human\u2019s","volume":"4","author":"Sengupta","year":"2013","journal-title":"Int. J. Prev. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"703527","DOI":"10.3389\/fimmu.2021.703527","article-title":"Microglia, Cytokines, and Neural Activity: Unexpected Interactions in Brain Development and Function","volume":"12","author":"Ferro","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"499-e1","DOI":"10.1016\/j.ajog.2012.10.005","article-title":"Neuroprotective peptides influence cytokine and chemokine alterations in a model of fetal alcohol syndrome","volume":"207","author":"Roberson","year":"2012","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1002\/eji.1830190418","article-title":"On the cellular source and function of interleukin 6 produced in the central nervous system in viral diseases","volume":"19","author":"Frei","year":"1989","journal-title":"Eur. J. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/0304-3940(89)90600-9","article-title":"Interleukin-6 as a neurotrophic factor for promoting the survival of cultured basal forebrain cholinergic neurons from postnatal rats","volume":"104","author":"Hama","year":"1989","journal-title":"Neurosci. Lett."},{"key":"ref_79","first-page":"3546","article-title":"Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor 2\/interleukin 6","volume":"8","author":"Satoh","year":"1988","journal-title":"Mol. Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1542\/peds.2003-0494-F","article-title":"Does interleukin-6 genotype influence cerebral injury or developmental progress after preterm birth?","volume":"114","author":"Harding","year":"2004","journal-title":"Pediatrics"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.bbadis.2012.01.011","article-title":"Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors","volume":"1822","author":"Wei","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e199","DOI":"10.1038\/tp.2012.120","article-title":"Evidence for sustained elevation of IL-6 in the CNS as a key contributor of depressive-like phenotypes","volume":"2","author":"Neal","year":"2012","journal-title":"Transl. Psychiatry"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.imlet.2007.07.010","article-title":"The allergic cascade: Review of the most important molecules in the asthmatic lung","volume":"113","author":"Bloemen","year":"2007","journal-title":"Immunol. Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/0167-5699(91)90120-I","article-title":"Human TH1 and TH2 subsets: Doubt no more","volume":"12","author":"Romagnani","year":"1991","journal-title":"Immunol. Today"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1111\/pai.13099","article-title":"Adverse health outcomes associated with fetal alcohol exposure: A systematic review focused on immune-related outcomes","volume":"30","author":"Reid","year":"2019","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1111\/j.1365-2362.2009.02190.x","article-title":"Choline supplementation reduces oxidative stress in mouse model of allergic airway disease","volume":"39","author":"Mehta","year":"2009","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.imbio.2009.09.004","article-title":"Choline attenuates immune inflammation and suppresses oxidative stress in patients with asthma","volume":"215","author":"Mehta","year":"2010","journal-title":"Immunobiology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3389\/fncel.2016.00169","article-title":"Allergy Enhances Neurogenesis and Modulates Microglial Activation in the Hippocampus","volume":"10","author":"Klein","year":"2016","journal-title":"Front. Cell Neurosci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"111813","DOI":"10.1016\/j.biopha.2021.111813","article-title":"Cannabidiol attenuates cognitive deficits and neuroinflammation induced by early alcohol exposure in a mice model","volume":"141","author":"Valverde","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"152958","DOI":"10.1016\/j.tox.2021.152958","article-title":"Aberrant neurogenesis and late onset suppression of synaptic plasticity as well as sustained neuroinflammation in the hippocampal dentate gyrus after developmental exposure to ethanol in rats","volume":"462","author":"Takahashi","year":"2021","journal-title":"Toxicology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1111\/acer.13021","article-title":"Adolescent Choline Supplementation Attenuates Working Memory Deficits in Rats Exposed to Alcohol during the Third Trimester Equivalent","volume":"40","author":"Schneider","year":"2016","journal-title":"Alcohol Clin. Exp. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1189\/jlb.0603252","article-title":"Interferon-gamma: An overview of signals, mechanisms and functions","volume":"75","author":"Schroder","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.1002\/glia.23878","article-title":"Priming of microglia with IFN-gamma impairs adult hippocampal neurogenesis and leads to depression-like behaviors and cognitive defects","volume":"68","author":"Zhang","year":"2020","journal-title":"Glia"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e707","DOI":"10.1038\/tp.2015.194","article-title":"Absence of IFNgamma promotes hippocampal plasticity and enhances cognitive performance","volume":"6","author":"Monteiro","year":"2016","journal-title":"Transl. Psychiatry"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"392","DOI":"10.3346\/jkms.2009.24.3.392","article-title":"The effect of rush immunotherapy with house dust mite in the production of IL-5 and IFN-gamma from the peripheral blood T cells of asthmatic children","volume":"24","author":"Kim","year":"2009","journal-title":"J. Korean Med. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1111\/j.1399-3038.2009.00865.x","article-title":"Maturation of cytokine-producing capacity from birth to 1 yr of age","volume":"20","author":"Lappalainen","year":"2009","journal-title":"Pediatr Allergy Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.3945\/ajcn.114.099168","article-title":"Choline supplementation in children with fetal alcohol spectrum disorders: A randomized, double-blind, placebo-controlled trial","volume":"102","author":"Wozniak","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nri.2016.123","article-title":"Cytokine networks in neuroinflammation","volume":"17","author":"Becher","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.neubiorev.2014.05.012","article-title":"The role of nicotinic receptors in shaping and functioning of the glutamatergic system: A window into cognitive pathology","volume":"46","author":"Molas","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.bbr.2009.12.049","article-title":"Developmental aspects of the cholinergic system","volume":"221","author":"Filgueiras","year":"2011","journal-title":"Behav. Brain Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1002\/(SICI)1098-1063(2000)10:1<94::AID-HIPO11>3.0.CO;2-T","article-title":"Effects of prenatal alcohol exposure on the hippocampus: Spatial behavior, electrophysiology, and neuroanatomy","volume":"10","author":"Berman","year":"2000","journal-title":"Hippocampus"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.yhbeh.2010.08.007","article-title":"Prenatal alcohol exposure reduces the proportion of newly produced neurons and glia in the dentate gyrus of the hippocampus in female rats","volume":"58","author":"Uban","year":"2010","journal-title":"Horm. Behav."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/j.1530-0277.2011.01644.x","article-title":"A limited access mouse model of prenatal alcohol exposure that produces long-lasting deficits in hippocampal-dependent learning and memory","volume":"36","author":"Brady","year":"2012","journal-title":"Alcohol Clin. Exp. 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