Journal article
Regional Patterns of Alcohol-Induced Neuronal Loss Depend on Genetics: Implications for Fetal Alcohol Spectrum Disorder
Alcoholism, clinical and experimental research, Vol.42(9), pp.1627-1639
09/2018
DOI: 10.1111/acer.13824
PMCID: PMC6445660
PMID: 29957842
Abstract
Alcohol exposure during pregnancy can kill developing neurons and lead to fetal alcohol spectrum disorder (FASD). However, affected individuals differ in their regional patterns of alcohol-induced neuropathology. Because neuroprotective genes are expressed in spatially selective ways, their mutation could increase the vulnerability of some brain regions, but not others, to alcohol teratogenicity. The objective of this study was to determine whether a null mutation of neuronal nitric oxide synthase (nNOS) can increase the vulnerability of some brain regions, but not others, to alcohol-induced neuronal losses.
Immunohistochemistry identified brain regions in which nNOS is present or absent throughout postnatal development. Mice genetically deficient for nNOS (nNOS
) and wild-type controls received alcohol (0.0, 2.2, or 4.4 mg/g/d) over postnatal days (PD) 4 to 9. Mice were sacrificed in adulthood (~PD 115), and surviving neurons in the olfactory bulb granular layer and brain stem facial nucleus were quantified stereologically.
nNOS was expressed throughout postnatal development in olfactory bulb granule cells but was never expressed in the facial nucleus. In wild-type mice, alcohol reduced neuronal survival to similar degrees in both cell populations. However, null mutation of nNOS more than doubled alcohol-induced cell death in the olfactory bulb granule cells, while the mutation had no effect on the facial nucleus neurons. As a result, in nNOS
mice, alcohol caused substantially more cell loss in the olfactory bulb than in the facial nucleus.
Mutation of the nNOS gene substantially increases vulnerability to alcohol-induced cell loss in a brain region where the gene is expressed (olfactory bulb), but not in a separate brain region, where the gene is not expressed (facial nucleus). Thus, differences in genotype may explain why some individuals are vulnerable to FASD, while others are not, and may determine the specific patterns of neuropathology in children with FASD.
Details
- Title: Subtitle
- Regional Patterns of Alcohol-Induced Neuronal Loss Depend on Genetics: Implications for Fetal Alcohol Spectrum Disorder
- Creators
- Dylan Todd - Neuroscience Program , Carver College of Medicine, University of Iowa, Iowa City, IowaDaniel J Bonthius Jr - Department of Biology , Wartburg College, Waverly, IowaLia Marie Sabalo - Department of Pediatrics , Carver College of Medicine, University of Iowa, Iowa City, IowaJasmine Roghair - Department of Pediatrics , Carver College of Medicine, University of Iowa, Iowa City, IowaBahri Karacay - Department of Pediatrics , Carver College of Medicine, University of Iowa, Iowa City, IowaSamantha Larimer Bousquet - Department of Biology , Wartburg College, Waverly, IowaDaniel J Bonthius - Department of Neurology , Carver College of Medicine, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Alcoholism, clinical and experimental research, Vol.42(9), pp.1627-1639
- DOI
- 10.1111/acer.13824
- PMID
- 29957842
- PMCID
- PMC6445660
- NLM abbreviation
- Alcohol Clin Exp Res
- ISSN
- 0145-6008
- eISSN
- 1530-0277
- Publisher
- Wiley; England
- Grant note
- T35 HL007485 / NHLBI NIH HHS R01 AA021465 / NIAAA NIH HHS R21 AA018711 / NIAAA NIH HHS T32 GM007337 / NIGMS NIH HHS
- Language
- English
- Date published
- 09/2018
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984065738402771
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