Timing of Moderate Level Prenatal Alcohol Exposure Influences Gene Expression of Sensory Processing Behavior in Rhesus Monkeys

Department of Kinesiology, University of Wisconsin-Madison Madison, WI, USA.
Frontiers in Integrative Neuroscience 11/2009; 3:30. DOI: 10.3389/neuro.07.030.2009
Source: PubMed


Sensory processing disorder, characterized by over- or under-responsivity to non-noxious environmental stimuli, is a common but poorly understood disorder. We examined the role of prenatal alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and striatal dopamine (DA) function on behavioral measures of sensory responsivity to repeated non-noxious sensory stimuli in macaque monkeys. Results indicated that early gestation alcohol exposure induced behavioral under-responsivity to environmental stimuli in monkeys carrying the short (s) rh5-HTTLPR allele compared to both early-exposed monkeys homozygous for the long (l) allele and monkeys from middle-to-late exposed pregnancies and controls, regardless of genotype. Moreover, prenatal timing of alcohol exposure altered the relationship between sensory scores and DA D(2)R availability. In early-exposed monkeys, a positive relationship was shown between sensory scores and DA D(2)R availability, with low or blunted DA function associated with under-responsive sensory function. The opposite pattern was found for the middle-to-late gestation alcohol-exposed group. These findings raise questions about how the timing of prenatal perturbation and genotype contributes to effects on neural processing and possibly alters neural connections.

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    • "A number of genes have also been identified as potentially playing a direct role in FASD. In a study of rhesus monkeys, it was demonstrated that fetal monkeys carrying a short serotonin transporter gene polymorphic region variation (rh5-HTTLPR), an allele with a functional analog in humans, were particularly susceptible to prenatal alcohol exposure during early gestation, leading to sensory disorders (Schneider et al., 2009). Prior studies indicated that this allele was linked to a greater incidence of irritability and stress-responsiveness in monkey offspring subjected to prenatal alcohol exposure (Kraemer et al., 2008). "
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    ABSTRACT: Fetal alcohol spectrum disorders (FASD) are a group of related conditions that arise from prenatal exposure to maternal consumption of the teratogen, ethanol. It has been estimated that roughly 1% of children in the US suffer from FASD (Sampson etal., 1997), though in some world populations, such as inhabitants of some poorer regions of South Africa, the rate can climb to as high as 20% (May etal., 2013). FASD are the largest cause of mental retardation in U.S. neonates, and ironically, are entirely preventable. FASD have been linked to major changes in the hypothalamic-pituitary-adrenal (HPA) axis, resulting in lifelong impairments through mental disorders, retardation, and sensitivity to stress. FASD are linked to an impaired immune system which consequently leads to an elevated risk of cancer and other diseases. FASD arise from a complex interplay of genetic and epigenetic factors. Here, we review current literature on the topic to tease apart what is known in these areas particularly emphasizing HPA axis dysfunction and how this ties into new studies of transgenerational inheritance in FASD.
    Full-text · Article · Jun 2014 · Frontiers in Genetics
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    • "It has been shown using both non-human primates [111] [112] [113] and rodent models as well as in humans [50] that prenatal exposure to alcohol impairs habituation to external stimuli, requiring more trials to habituate to olfactory, visual, tactile or auditory stimuli, which suggest impairment in the regulatory brain mechanisms. Schneider and colleagues [111] [112], in a study using non-human primates, reported that animals submitted to alcohol exposure presented an exacerbated response to sensory (tactile) stimuli in adulthood. Similar results were observed in children who had FAS [114]. "

    Full-text · Chapter · Jan 2014
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    • "It has been shown that the timing of heavy episodes of alcohol consumption during pregnancy may determine which functional system may be affected depending on the cytoarchitectonic areas that are at the peak of neuronal migration at that period (Sidman and Rakic 1973). Furthermore , the timing of the prenatal alcohol exposure may alter gene expression (Schneider et al. 2009; Hashimoto-Torii et al. 2011) and differentially affect both neural migration and differentiation. Future studies with detailed information on the amount, frequency, and timing of prenatal alcohol use can advance our understanding on the teratogenic effect of alcohol on the brain, though this information is rarely available in human populations. "
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    ABSTRACT: Accumulating evidence from structural brain imaging studies on individuals with fetal alcohol spectrum disorder (FASD) has supported links between prenatal alcohol exposure and brain morphological deficits. Although global and regional volumetric reductions appear relatively robust, the effects of alcohol exposure on cortical thickness and relationships with facial dysmorphology are not yet known. The structural magnetic resonance imaging data from 69 children and adolescents with FASD and 58 nonexposed controls collected from 3 sites were examined using FreeSurfer to detect cortical thickness changes across the entire brain in FASD and their associations with facial dysmorphology. Controlling for brain size, subjects with FASD showed significantly thicker cortices than controls in several frontal, temporal, and parietal regions. Analyses conducted within site further revealed prominent group differences in left inferior frontal cortex within all 3 sites. In addition, increased inferior frontal thickness was significantly correlated with reduced palpebral fissure length. Consistent with previous reports, findings of this study are supportive of regional increases in cortical thickness serving as a biomarker for disrupted brain development in FASD. Furthermore, the significant associations between thickness and dysmorphic measures suggest that the severity of brain anomalies may be reflected by that of the face.
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