Alcohol exposure during development: Impact on the epigenome

Abstract

Fetal alcohol spectrum disorders represent a wide range of symptoms associated with in utero alcohol exposure. Animal models of FASD have been useful in determining the specific neurological consequences of developmental alcohol exposure, but the mechanisms of those consequences are unclear. Long-lasting changes to the epigenome are proposed as a mechanism of alcohol-induced teratogenesis in the hippocampus. The current study utilized a three-trimester rodent model of FASD to examine changes to some of the enzymatic regulators of the epigenome in adolescence. Combined pre- and post-natal alcohol exposureresulted in a significant increase in DNA methyltransferase activity (DNMT), without affecting histone deacetylase activity (HDAC). Developmental alcohol exposure also caused a change in gene expression of regulators of the epigenome, in particular, DNMT1, DNMT3a, and methyl CpG binding protein 2 (MeCP2). The modifications of the activity and expression of epigenetic regulators in the hippocampus of rodents perinatally exposed to alcohol suggest that alcohol's impact on the epigenome and its regulators may be one of the underlying mechanisms of alcohol teratogenesis.

Keywords: ARND; BAC; BDNF; CNS; CT; DMR; DNA methyltransferase; DNMT; ET; Epigenetics; FAS; FASD; Fetal alcohol spectrum disorders; GD; HAT; HDAC; Hippocampus; IC; MBDs; MeCP2; NC; PD; PFC; alcohol-related neurodevelopmental disorder; blood alcohol concentration; brain-derived neurotrophic factor; central nervous system; crossing threshold; differentially methylated region; ethanol-exposed group; fetal alcohol spectrum disorder; fetal alcohol syndrome; gestational day; histone acetyltransferase; histone deacetylase; intubated control group; methyl CpG binding protein 2; methyl binding domains; non-treated control group; postnatal day; prefrontal cortex.

Figure 1. Average DNA methyltransferase activity (±SEM) in the hippocampus

Data are collapsed across sex and error bars represent SEM. The four-pointed star indicates a significant difference (p<0.05) between the ethanol-exposed group and the intubated control group. The five-pointed star indicates a significant difference between the ethanol-exposed group and the non-treated control group.

Figure 2. Average Histone Deacetylase (HDAC) activity (±SEM) in the hippocampus

Data are collapsed across sex and error bars represent SEM. There were no significant differences among any treatment groups.