Original Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756137/
- The unfavorable effects of alcohol consumption during pregnancy have long been known.
- A formal description and clinical diagnosis of these effects was in 1973.
- The distinction of the wide range of effects that can be caused by prenatal alcohol exposure and the terminology to describe these effects has continued to change.
- Much progress has been made in understanding the consequences of alcohol exposure during pregnancy.
- However, challenges still remain in properly identifying all affected individuals as well as their individual patterns of deficiency induced by alcohol.
- The number of pregnant women who drink alcohol continues to increase.
- Alcohol-consumption prevention efforts still require further improvement to amplify their effectiveness.
- The mechanisms underlying damage induced by alcohol have not yet been fully explained.
- Knowledge of the mechanisms underlying alcohol-induced deficiency continues to grow.
- The possibility of minimizing potential harm by intervening during prenatal alcohol exposure is enhanced.
- Researchers are exploring additional ways to improve or fully restore behavioral and cognitive functions disrupted by prenatal alcohol exposure.
- The exploration for improvements/restorations includes treating the individuals with fetal alcohol spectrum disorders to reduce the heavy burden for affected individuals and their families.
Background: Fetal alcohol spectrum disorder (FASD) is a leading cause of neurodevelopmental disorders. Children in foster care or domestically adopted are at greater risk for FASD. The aim of this study was to determine the prevalence or risk for FASD in a selected population of foster and adopted children.
Hippocampal transcriptome analysis following maternal separation implicates altered RNA processing in a mouse model of fetal alcohol spectrum disorder
Background: Fetal alcohol spectrum disorders (FASD) are common, seen in 1-5% of the population in the USA and Canada. Children diagnosed with FASD are not likely to remain with their biological parents, facing early maternal separation and foster placements throughout childhood.
A randomized controlled trial of transcranial direct-current stimulation and cognitive training in children with fetal alcohol spectrum disorder
Background: This study was a randomized double-blind sham-controlled trial examining the effects of transcranial direct current stimulation (tDCS) augmented cognitive training (CT) in children with Fetal Alcohol Spectrum Disorders (FASD). Prenatal alcohol exposure has profound detrimental effects on brain development and individuals with FASD commonly present with deficits in executive functions including attention and working memory. The most commonly studied treatment for executive deficits is CT, which involves repeated drilling of exercises targeting the impaired functions. As currently implemented, CT requires many hours and the observed effect sizes are moderate. Neuromodulation via tDCS can enhance brain plasticity and prior studies demonstrate that combining tDCS with CT improves efficacy and functional outcomes. TDCS-augmented CT has not yet been tested in FASD, a condition in which there are known abnormalities in neuroplasticity and few interventions.
Prenatal alcohol exposure (PAE) affects at least 10% of newborns globally and leads to the development of fetal alcohol spectrum disorders (FASDs). Despite its high incidence, there is no consensus on the implications of PAE on metabolic disease risk in adults. Here, we describe a cohort of adults with FASDs that had an increased incidence of metabolic abnormalities, including type 2 diabetes, low HDL, high triglycerides, and female-specific overweight and obesity. Using a zebrafish model for PAE, we performed population studies to elucidate the metabolic disease seen in the clinical cohort. Embryonic alcohol exposure (EAE) in male zebrafish increased the propensity for diet-induced obesity and fasting hyperglycemia in adulthood. We identified several consequences of EAE that may contribute to these phenotypes, including a reduction in adult locomotor activity, alterations in visceral adipose tissue and hepatic development, and persistent diet-responsive transcriptional changes. Taken together, our findings define metabolic vulnerabilities due to EAE and provide evidence that behavioral changes and primary organ dysfunction contribute to resultant metabolic abnormalities.
Keywords: Development; Embryonic development; Metabolism; Obesity.
Hippocampal DNA Methylation in a Mouse Model of Fetal Alcohol Spectrum Disorder That Includes Maternal Separation Stress Only Partially Explains Changes in Gene Expression
Fetal alcohol spectrum disorder (FASD) is characterized by developmental and behavioral deficits caused by maternal drinking during pregnancy. Children born with FASD often face additional stresses, including maternal separation, that add yet additional deficits. The mechanism associated with this interaction is not known. We have used a mouse model for prenatal ethanol exposure and maternal separation to demonstrate that the combination of the two treatments results in more than additive deficits. Furthermore, the behavioral deficits are associated with changes in hippocampal gene expression that persist into adulthood. What initiates and maintains these changes remains to be established and forms the focus of this report. Specifically, MeDIP-Seq was used to assess if changes in promoter DNA methylation are affected by exposure to prenatal ethanol and maternal separation including its relationship to gene expression. The novel results show that different sets of genes implicated by promoter DNA methylation are affected by both treatments independently, and a relatively unique set of genes are affected by the combination of the two treatments. Prenatal ethanol exposure leads to altered promoter DNA methylation at genes important for transcriptional regulation. Maternal separation leads to changes at genes important for histone methylation and immune response, and the combination of two treatments results in DNA methylation changes at genes important for neuronal migration and immune response. Our dual results from the same hippocampal samples suggest there is minimal complementarity between changes in promoter DNA methylation and gene expression, although genes involved tend to be critical for brain development and function. While remaining to be validated, such results argue that mechanisms beyond promoter DNA methylation must be involved in lasting gene expression alterations leading to behavioral deficits implicated in FASD. They may facilitate early and reliable diagnosis, as well as novel strategies for the amelioration of FASD-related deficits.
Keywords: fetal alcohol spectrum disorder; DNA methylation; early life stress; hippocampus; maternal separation; prenatal alcohol.