Abstract

BackgroundChildren whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood.ResultsMice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks.ConclusionsUsing a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development.

Highlights

  • Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances

  • Fetal alcohol exposure reduces olfactory bulbs (OB) neurogenesis during early postnatal development As the OB is one of the brain regions to which new neurons continue to be added after birth and into adulthood [20,21], we investigated whether deficits in postnatal neurogenesis may contribute to the reduced

  • Using high-resolution magnetic resonance imaging (MRI), we observed both increases and decreases in the size of particular brain regions, including the basal forebrain, anterior commissure, amygdala, and the granule cell layer of the dentate gyrus. Amid these widespread changes in brain volume, the largest reduction in volume occurred in the OB. We found that this decrease in OB volume during adulthood may arise from deficits in OB neurogenesis occurring during early development, as mice with fetal alcohol exposure possessed fewer neural progenitor cells in the subependymal zone (SEZ) and fewer new cells in the granule cell layer of the OB during the first few postnatal weeks, but normal numbers of new cells in the OB during adulthood

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Summary

Introduction

Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. We used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. The high incidence of FASD warrants further study into its biological basis and behavioral manifestations, but it is often difficult to disentangle the links between gestational alcohol exposure and developmental abnormalities. Many difficulties inherent in human studies, can be overcome by animal models of fetal alcohol exposure [14], which allow for control over the amount and timing of alcohol intake as well as the isolation of drinking from other confounding factors. Animal models provide opportunities to investigate the neurobiological mechanisms underlying fetal alcohol effects and to determine if those effects persist across the lifespan

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