Journal article
Severe alcohol‐induced neuronal deficits in the hippocampus and neocortex of neonatal mice genetically deficient for neuronal nitric oxide synthase (nNOS)
Journal of comparative neurology (1911), Vol.499(2), pp.290-305
11/10/2006
DOI: 10.1002/cne.21095
PMID: 16977619
Abstract
Alcohol can severely damage the developing brain, and neuronal loss is a critical component of this injury. Thus, identification of molecular factors that ameliorate alcohol‐induced neuronal loss is of great importance. Previous in vitro work has demonstrated that nitric oxide (NO) protects neurons against alcohol toxicity. We tested the hypothesis that neonatal mice carrying a null mutation for neuronal nitric oxide synthase (nNOS), the enzyme that synthesizes NO in neurons, have an increased vulnerability to alcohol‐induced neuronal loss in the neocortex and hippocampus. Wildtype mice and nNOS−/− mice received ethanol (0.0, 2.2, 3.3, or 4.4 g/kg) daily over postnatal days (P) 4–9 and were sacrificed on P10. The number of hippocampal CA1 and CA3 pyramidal cells, dentate gyrus granule cells, and neocortical neurons were determined using stereological methods. Alcohol pharmacokinetics did not differ between wildtype and nNOS−/− strains. Alcohol induced dose‐dependent reductions in all four neuronal populations, and the losses were substantially more severe in the nNOS−/− mice than in wildtype. Furthermore, the threshold dose of alcohol to induce cell death was lower in the nNOS−/− mice than in the wildtype mice for all neuronal populations. While nNOS deficiency worsened alcohol‐induced neuronal losses, the magnitude of this exacerbation varied among brain regions and depended on alcohol dose. These results demonstrate that nNOS deficiency decreases the ability of developing neurons in vivo to survive the toxic effects of alcohol and strengthen the hypothesis that NO exerts a neuroprotective effect against alcohol toxicity in the developing brain. J. Comp. Neurol. 499:290–305, 2006. © 2006 Wiley‐Liss, Inc.
Details
- Title: Subtitle
- Severe alcohol‐induced neuronal deficits in the hippocampus and neocortex of neonatal mice genetically deficient for neuronal nitric oxide synthase (nNOS)
- Creators
- Daniel J BonthiusRoss A MCkimLindsey KoeleHarb HarbAna Hutton KehrbergJo MahoneyBahri KaracayNicholas J Pantazis
- Resource Type
- Journal article
- Publication Details
- Journal of comparative neurology (1911), Vol.499(2), pp.290-305
- Publisher
- Wiley Subscription Services, Inc., A Wiley Company; Hoboken
- DOI
- 10.1002/cne.21095
- PMID
- 16977619
- ISSN
- 0021-9967
- eISSN
- 1096-9861
- Number of pages
- 16
- Grant note
- National Institutes of Health (NIH) (AA011577; NS02007; AA015747) Children's Miracle Network Carver Collaborative Research Grant
- Language
- English
- Date published
- 11/10/2006
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984065833402771
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