Fig. 5 | Translational Psychiatry

Fig. 5

From: The lncRNA BDNF-AS is an epigenetic regulator in the human amygdala in early onset alcohol use disorders

Fig. 5

Proposed association of regulation of decreased BDNF expression by BDNF-AS through recruitment of the PRC2 complex in the human amygdala of individuals who began drinking in adolescence. Adolescent drinking appears to increase the expression of BDNF-AS most likely via inhibition of RNA methylation. This is associated with decreases in BDNF expression in the amygdala via recruitment of EZH2 and the associated increase in H3K27 trimethylation (H3K27me3) at the promoter and overlap region of BDNF exon IX. Interestingly, the reduction in BDNF expression is associated with a reduction in activity-regulated cytoskeleton-associated protein (ARC) expression, possibly via an increase in occupancy of EZH2 and H3K27me3 at an important regulatory site of the ARC gene known as synaptic activity response element (SARE). These BDNF-AS-regulated epigenetic mechanisms induced by adolescent drinking in humans appears to be important in the pathophysiology of alcohol use disorders (AUD) later in life