Genetic Absence of nNOS Worsens Fetal Alcohol Effects in Mice. I: Behavioral Deficits.
Background Alcohol abuse during pregnancy often induces neuropsychological problems in the offspring, including learning disorders, attention deficits, and behavior problems, all of which are prominent components of fetal alcohol spectrum disorders (FASD). However, not all children who were exposed...
| Published in: | Alcoholism: Clinical & Experimental Research Vol. 39; no. 2; pp. 212 - 221 |
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| Main Authors: | , , , |
| Format: | research tables/charts Journal Article |
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Wiley-Blackwell
Feb2015
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=103759139&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 103759139 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 01456008 IQE jtl: Alcoholism: Clinical & Experimental Research issn: 01456008 maglogo: Y pubinfo: dt: Feb2015 vid: 39 iid: 2 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 103759139 100989513 100989513 10.1111/acer.12616 NLM25684045 103759139 ppf: 212 ppct: 9 formats: tig: atl: Genetic Absence of nNOS Worsens Fetal Alcohol Effects in Mice. I: Behavioral Deficits. aug: au: Karacay, Bahri Bonthius, Nancy E. Plume, Jeffrey Bonthius, Daniel J. affil: Department of Pediatrics, University of Iowa College of Medicine sug: subj: Oxidoreductases Nitric Oxide Fetal Alcohol Syndrome Familial and Genetic Behavior, Animal Ethanol Administration and Dosage Genes Animal Studies Rats Learning Brain Analysis of Variance Multivariate Analysis of Variance Post Hoc Analysis Data Analysis Software Repeated Measures Descriptive Statistics Funding Source ab: Background Alcohol abuse during pregnancy often induces neuropsychological problems in the offspring, including learning disorders, attention deficits, and behavior problems, all of which are prominent components of fetal alcohol spectrum disorders (FASD). However, not all children who were exposed to alcohol in utero are equally affected by it. While some children have major deficits, others are spared. This unequal vulnerability is likely due largely to differences in fetal genetics. Some fetuses appear to have certain genotypes that make them much more prone to FASD. However, to date, no gene has been identified that worsens alcohol-induced brain dysfunction. Nitric oxide (NO) is a gaseous molecule that can protect developing neurons against alcohol-induced death. In the brain, NO is produced by neuronal nitric oxide synthase ( nNOS). In this study, we examined whether homozygous mutation of the nNOS gene in mice worsens the behavioral deficits of developmental alcohol exposure. Methods Wild-type and nNOS−/− mice received alcohol (0.0, 2.2, or 4.4 mg/g) daily over postnatal days (PDs) 4 to 9. Beginning on PD 85, the mice underwent a series of behavioral tests, including open field activity, the Morris water maze, and paired pulse inhibition. Results For the wild-type mice, alcohol impaired performance only in the water maze. In contrast, for the nNOS−/− mice, alcohol impaired performance on all 3 tasks. Furthermore, the nNOS−/− mice were substantially more impaired than wild-type mice in their performance on all 3 of the behavioral tests and at both the low (2.2) and high (4.4) doses of alcohol. Conclusions Targeted disruption of the nNOS gene worsens the behavioral impact of developmental alcohol exposure and allows alcohol-induced learning problems to emerge that are not seen in wild type. This is the first demonstration that a specific genotype can interact with alcohol to worsen functional brain deficits in an animal model of FASD. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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