Chunk #89 — Future Directions: Combining Stress and Alcohol Models and Assessment of Multigenerational Effects and Therapeutics — Therapeutic Strategies
Because of data showing that developmental alcohol and stress act through epigenetic pathways, targeted pharmacological treatments that affect the epigenome hold promise for successful intervention. Adult rats exposed to caregiver maltreatment during the first week of postnatal life demonstrated a rescue of maltreatment-induced DNA methylation of the Bdnf gene after treatment with the DNMT inhibitor zebularine (Roth et al., 2009a). Antidepressants have been shown to rescue the depressive-like phenotype and epigenetic marks resulting from maternal separation (Ignácio et al., 2017; Park et al., 2017; Seo et al., 2016). In humans, adults that showed a positive response to treatment with the antidepressant citalopram showed normalized levels of BDNF and reduced levels of a repressive histone mark (H3K27me3) at the BDNF exon IV promoter (Lopez et al., 2013). While limited work has been done in PAE models, direct regulation of enzymatic activity through histone deacetylase (HDAC) inhibitors are a pharmacological avenue worth exploring. HDACs act to remove acetylation marks from histones, resulting in a more closed chromatin structure and reduced transcriptional activity (Abel and Zukin, 2008). HDAC inhibitors prevent these enzymes from
