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Magnetic Resonance Microscopy-based Analyses of the Neuroanatomical Effects of Gestational Day 9 Ethanol Exposure in Mice

Institution:
1Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA. Electronic address: sparnell@med.unc.edu.
2Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA.
3Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
Publisher:
Elsevier Science
Publication Date:
Sep-2013
Journal:
Neurotoxicol Teratol
Volume Number:
39
Pages:
77-83
Citation:
Neurotoxicol Teratol. 2013 Sep-Oct;39:77-83.
PubMed ID:
23911654
PMCID:
PMC3795920
Keywords:
Brain, Ethanol, Fetal alcohol spectrum disorder, MRI, Mouse, Shape analysis
Appears in Collections:
NA-MIC, SLICER
Sponsors:
K99 AA018697/AA/NIAAA NIH HHS/United States
P30 HD003110/HD/NICHD NIH HHS/United States
P41 EB015897/EB/NIBIB NIH HHS/United States
P60 AA011605/AA/NIAAA NIH HHS/United States
U01 AA017124/AA/NIAAA NIH HHS/United States
U01 A0021651/AA/NIAAA NIH HHS/United States
U54 EB005149/EB/NIBIB NIH HHS/United States
Generated Citation:
Parnell S.E., Holloway H.T., O'Leary-Moore S.K., Dehart D.B., Paniaqua B., Oguz I., Budin F., Styner M., Johnson G.A., Sulik K.K. Magnetic Resonance Microscopy-based Analyses of the Neuroanatomical Effects of Gestational Day 9 Ethanol Exposure in Mice. Neurotoxicol Teratol. 2013 Sep-Oct;39:77-83. PMID: 23911654. PMCID: PMC3795920.
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Animal model-based studies have shown that ethanol exposure during early gestation induces developmental stage-specific abnormalities of the face and brain. The exposure time-dependent variability in ethanol's teratogenic outcomes is expected to contribute significantly to the wide spectrum of effects observed in humans with fetal alcohol spectrum disorder (FASD). The work presented here employs a mouse FASD model and magnetic resonance microscopy (MRM; high resolution magnetic resonance imaging) in studies designed to further our understanding of the developmental stage-specific defects of the brain that are induced by ethanol. At neurulation stages, i.e. at the beginning of gestational day (GD) 9 and again 4 hours later, time-mated C57Bl/6J dams were intraperitoneally administered 2.9 g/kg ethanol or vehicle. Ethanol-exposed fetuses were collected on GD 17, processed for MRM analysis, and results compared to comparably staged controls. Linear and volume measurements as well as shape changes for numerous individual brain regions were determined. GD 9 ethanol exposure resulted in significantly increased septal region width, reduction of cerebellar volume, and enlargement of all of the ventricles. Additionally, the results of shape analyses showed that many areas of the ethanol-exposed brains including the cerebral cortex, hippocampus and right striatum were significantly misshapen. These data demonstrate that ethanol can induce dysmorphology that may not be obvious based on volumetric analyses alone, highlight the asymmetric aspects of ethanol-induced defects, and add to our understanding of ethanol's developmental stage-dependent neuroteratogenesis.

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