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Brain Res. 2012 Jun 6;1458:18-33. doi: 10.1016/j.brainres.2012.04.016. Epub 2012 Apr 17.

Long-term alterations to the brain transcriptome in a maternal voluntary consumption model of fetal alcohol spectrum disorders.

Author information

1
Molecular Genetics Unit, Department of Biology, University of Western Ontario, London, Ontario, Canada N6A 5B7.

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.

PMID:
22560501
DOI:
10.1016/j.brainres.2012.04.016
[Indexed for MEDLINE]

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