Characterizing BDNF Methylation in the Adult Insula Following Early-Life Caregiver Maltreatment In Rats
Date
2016-05
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Publisher
University of Delaware
Abstract
Adverse caregiving early in life can result in long-lasting changes in brain function and behavior and has been linked to aberrant behavioral outcomes and psychopathology later in life. Animal models have shown similar changes and outcomes. One way that changes in brain and behavior are conferred by early life adversity is through epigenetic changes such as DNA methylation. DNA methylation is an epigenetic modification that can alter gene expression without changing the sequence of nucleotide bases and is generally associated with decreased gene expression. We have previously shown that rats exposed to a maltreatment regimen repeatedly throughout their first week of life have DNA methylation changes in the Brain-derived neurotrophic factor (Bdnf) gene in adulthood in the whole prefrontal cortex, medial prefrontal cortex, amygdala, and hippocampus. Bdnf plays an important role in neural development and plasticity and is implicated in various psychiatric disorders. The aim of the current study was to assess Bdnf methylation and gene expression changes in an additional brain region, the insula. The insula is involved in cognitive, sensory (i.e. soft stroking touch), and emotional domains in humans. It has alsobeen implicated in psychiatric disorders such as depression, anxiety, and mood disorders. Using a within-litter design, pups were exposed to an adverse (maltreatment) or nurturing (cross-foster care) caregiving environment outside of the home cage for 30 minutes a day for postnatal (PN) days 1-7. Remaining pups were left in the home cage with the biological mother. Brains were removed on PN 90 and DNA methylation and gene expression were measured for Bdnf exon IV. Results indicated that adult males nurtured early in life had less unmethylated Bdnf IV DNA, although this group had no changes in gene expression. Further, maltreated males had no changes in methylation but a significant decrease in Bdnf mRNA compared to normal controls. Although more analyses are needed to confirm methylation findings, these data suggest that the insula could be a new region of interest for stress-induced DNA methylation and/or gene expression changes.
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Keywords
neuroscience, caregiver maltreatment