Teenage drinking lnc’ed with epigenetic changes to emotional center of brain

From Genetic Engineering News

A study of human brain tissue has found that binge drinking during adolescence causes epigenetic changes that could be linked with the development of psychological problems and alcohol use disorder (AUD) in adulthood. The study, headed by researchers at the University of Illinois at Chicago (UIC) Center for Alcohol Research in Epigenetics, discovered that the brains of individuals who had started drinking before age 21 demonstrated epigenetic changes that altered the expression of a protein called brain-derived neurotrophic factor (BDNF), which is involved in the formation and maintenance of neural connections in the amygdala. This region of the brain controls emotions and decision making.

“The epigenetic changes we saw in the amygdala of early-onset drinkers can alter the normal function of the amygdala, which helps regulate our emotions, and may cause individuals to be more susceptible for things like anxiety, which we have shown in other studies, or the development and maintenance of alcohol use disorder later in life,” commented Subhash Pandey, PhD, professor of psychiatry and director of the UIC Center for Alcohol Research in Epigenetics. Pandey is corresponding author of the scientists’ published paper in Translational Psychiatry, which is titled, “The lncRNA BDNF-AS is an epigenetic regulator in the human amygdala in early onset alcohol use disorders.”

lncRNA

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

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Bohnsack JP, Teppen T, Kyzar EJ, Dzitoyeva S, Pandey SC. (2018) The lncRNA BDNF-AS is an epigenetic regulator in the human amygdala in early onset alcohol use disorders. Transl Psychiatry 9(1):34. [article]

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