Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice

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.

Alcohol exposure inhibits adult neural stem cell proliferation

“…The apparent resilience of the adult NSC pool to in vivo alcohol exposure contrasts in some respects with recent findings indicating that prenatal alcohol reduces the number of neurospheres in the neonatal SVZ (Akers et al, 2011; Rubert et al, 2006; Santillano et al, 2005). NSCs may be more sensitive to insults during embryonic expansion of the pool relative to the static population dynamics of adulthood, as has been demonstrated for other insults such as prenatal versus adult stress (Kippin et al, 2004).…”

Radiological studies of fetal alcohol spectrum disorders in humans and animal models: An updated comprehensive review

“…Ex vivo MRI at PD60 following PAE (10% v/v) throughout gestation revealed both increases and decreases in regional brain volumes in the offspring of 129Svev and C57Bl/6 mice, including decreased volumes of the olfactory bulbs, the granule cell layer of the dentate gyrus and the fourth ventricle; and increased volumes of the basal forebrain, the posterior part of the anterior commissure, the stria medullaris of the thalamus and the amygdala [166].…”

Ontogeny of contextual fear memory formation, specificity, and persistence in mice

“…We found no differences between groups in dam body weight at onset of pregnancy (control: 26.8 + 1.4 g, EtOH: 25.6 + 0.7 g), weight gained across pregnancy (control: 12.7 + 1.2 g, EtOH: 13.9 + 0.6 g), or litter size (control: 6.0 + 0.6 pups, EtOH: 6.7 + 0.4 pups). Previous studies have shown that this procedure has no effect on maternal behavior or pup body weight but produces changes in brain volume, levels of neurotrophic factors, and behavior that persist into adulthood (Allan et al 2003;Caldwell et al 2008;Akers et al 2011). …”

“…The fetal alcohol exposure procedure was adapted from previous studies (Allan et al 2003;Akers et al 2011). Briefly, female mice (n ¼ 10) were given saccharin-flavored drinking water (0.1% saccharin) to which ethanol (EtOH) was gradually introduced (0% EtOH for 4 d, 2% EtOH for 1 d, 5% for 1 d, 10% for 4 d).…”