title: Long-term alterations to the brain transcriptome in a maternal voluntary consumption model of fetal alcohol spectrum disorders.
abstract: Many women continue to consume low to moderate quantities of alcohol during pregnancy, which can result in the variable neurobehavioural effects in the absence of physiological abnormalities that characterize fetal alcohol spectrum disorders (FASD). Previously, we reported that a mouse model for FASD based on voluntary maternal ethanol consumption throughout gestation resulted in offspring that showed mild developmental delay, anxiety-related traits, and deficits in spatial learning. Here, we extend this model by evaluating the gene expression changes that occur in the adult brain of C57BL/6J mice prenatally exposed to ethanol via maternal preference drinking. The results of two independent expression array experiments indicate that ethanol induces subtle but consistent changes to global gene expression. Gene enrichment analysis showed over-represented gene ontology classifications of cellular, embryonic, and nervous system development. Molecular network analysis supported these classifications, with significant networks related to cellular and tissue development, free radical scavenging, and small molecule metabolism. Further, a number of genes identified have previously been implicated in FASD-relevant neurobehavioural phenotypes such as cognitive function (Ache, Bcl2, Cul4b, Dkc1, Ebp, Lcat, Nsdh1, Sstr3), anxiety (Bcl2), attention deficit hyperactivity disorder (Nsdh1), and mood disorders (Bcl2, Otx2, Sstr3). The results suggest a complex residual "footprint" of neurodevelopmental ethanol exposure that may provide a new perspective for identifying mechanisms that underlie the life-long persistence of FASD-related cognitive and behavioural alterations, including potential targets for treatment.
authors.affiliation: Molecular Genetics Unit, Department of Biology, University of Western Ontario, London, Ontario, Canada N6A 5B7.
authors.forename: Morgan L
authors.initials: ML
authors.lastname: Kleiber
authors.forename: Benjamin I
authors.initials: BI
authors.lastname: Laufer
authors.forename: Elise
authors.initials: E
authors.lastname: Wright
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Diehl
authors.forename: Shiva M
authors.initials: SM
authors.lastname: Singh
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics*; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000235:genetics* / Q000378:metabolism; D053263:Gene Regulatory Networks / Q000187:drug effects / Q000502:physiology; D008297:Male; D008425:Maternal Behavior / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D059467:Transcriptome / Q000187:drug effects* / Q000235:genetics
chemical_list: D000431:Ethanol