title: Prenatal ethanol exposure disrupts intraneocortical circuitry, cortical gene expression, and behavior in a mouse model of FASD.
abstract: In utero ethanol exposure from a mother's consumption of alcoholic beverages impacts brain and cognitive development, creating a range of deficits in the child (Levitt, 1998; Lebel et al., 2012). Children diagnosed with fetal alcohol spectrum disorders (FASD) are often born with facial dysmorphology and may exhibit cognitive, behavioral, and motor deficits from ethanol-related neurobiological damage in early development. Prenatal ethanol exposure (PrEE) is the number one cause of preventable mental and intellectual dysfunction globally, therefore the neurobiological underpinnings warrant systematic research. We document novel anatomical and gene expression abnormalities in the neocortex of newborn mice exposed to ethanol in utero. This is the first study to demonstrate large-scale changes in intraneocortical connections and disruption of normal patterns of neocortical gene expression in any prenatal ethanol exposure animal model. Neuroanatomical defects and abnormal neocortical RZRβ, Id2, and Cadherin8 expression patterns are observed in PrEE newborns, and abnormal behavior is present in 20-d-old PrEE mice. The vast network of neocortical connections is responsible for high-level sensory and motor processing as well as complex cognitive thought and behavior in humans. Disruptions to this network from PrEE-related changes in gene expression may underlie some of the cognitive-behavioral phenotypes observed in children with FASD.
authors.affiliation: Department of Psychology and Interdepartmental Neuroscience Program, University of California, Riverside, Riverside, California 92521.
authors.forename: Hani
authors.initials: H
authors.lastname: El Shawa
authors.forename: Charles W
authors.initials: CW
authors.lastname: Abbott
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Huffman
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002452:Cell Count; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000431:Ethanol / Q000097:blood; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology*; D015870:Gene Expression / Q000187:drug effects*; D066298:In Vitro Techniques; D051797:Inhibitor of Differentiation Protein 2 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008856:Microscopy, Fluorescence; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2 / Q000096:biosynthesis / Q000235:genetics; D009994:Osmolar Concentration; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology*; D015430:Weight Gain
chemical_list: D015820:Cadherins; C504541:Cdh8 protein, mouse; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2; C539741:Rorb protein, mouse; D000431:Ethanol