Alteration of Gene Expression, DNA Methylation, and Histone Methylation in Free Radical Scavenging Networks in Adult Mouse Hippocampus following Fetal Alcohol Exposure

<div><p>The molecular basis of Fetal Alcohol Spectrum Disorders (FASD) is poorly understood; however, epigenetic and gene expression changes have been implicated. We have developed a mouse model of FASD characterized by learning and memory impairment and persistent gene expression changes. Epigenetic marks may maintain expression changes over a mouse’s lifetime, an area few have explored. Here, mice were injected with saline or ethanol on postnatal days four and seven. At 70 days of age gene expression microarray, methylated DNA immunoprecipitation microarray, H3K4me3 and H3K27me3 chromatin immunoprecipitation microarray were performed. Following extensive pathway analysis of the affected genes, we identified the top affected gene expression pathway as “Free radical scavenging”. We confirmed six of these changes by droplet digital PCR including the caspase <i>Casp3</i> and Wnt transcription factor <i>Tcf7l2</i>. The top pathway for all methylation-affected genes was “Peroxisome biogenesis”; we confirmed differential DNA methylation in the <i>Acca1</i> thiolase promoter. Altered methylation and gene expression in oxidative stress pathways in the adult hippocampus suggests a novel interface between epigenetic and oxidative stress mechanisms in FASD.</p></div

Nutrigenomics as strategy for neuronal health

Nutrigenomics through gene expression and epigenetic remodeling can program adult health. Diet during pregnancy and lactation (the first 1000 days of life) can modulate offspring’s epigenome leading to tissue specific variations during cell differentiation processes, and may define epigenetic marks associated with longterm effects on offspring neuronal health. Being epigenetics reversible, a healthy diet represents a fundamental opportunity, even after the first 1000 days of life, for maintaining cellular homeostasis. The positive impact of food (i.e. maternal milk, oily fish, fruit and vegetables, curcumin, tea) with its dietary flavonoids (i.e. sulforaphane, quercetin, lutein, resveratrol, carotenoids) and other bioactive compounds (i.e. docosahexanoic acid, melatonin etc.), will be reflected on chromatin structure modulation and DNA methylation which are associated with switching on/off of genes. An anti-inflammatory diet during early-life and across the whole life may represent a key strategy for influencing brain plasticity and for building an “epigenetic memory” useful in developing neuronal resilience against early-life stressors and to prevent age-related neurodegeneration