The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking: A Translational Study.
Cerebral Cortex. 2019-02-04; 29(4): 1736-1751
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Alcohol abuse is a major public health problem worldwide. Understanding the
molecular mechanisms that control regular drinking may help to reduce hazards of
alcohol consumption. While immunological mechanisms have been related to alcohol
drinking, most studies reported changes in immune function that are secondary to
alcohol use. In this report, we analyse how the gene “TRAF family
member-associated NF-κB activator” (TANK) affects alcohol drinking behavior.
Based on our recent discovery in a large GWAS dataset that suggested an
association of TANK, SNP rs197273, with alcohol drinking, we report that SNP
rs197273 in TANK is associated both with gene expression (P = 1.16 × 10-19) and
regional methylation (P = 5.90 × 10-25). A tank knock out mouse model suggests a
role of TANK in alcohol drinking, anxiety-related behavior, as well as alcohol
exposure induced activation of insular cortex NF-κB. Functional and structural
neuroimaging studies among up to 1896 adolescents reveal that TANK is involved in
the control of brain activity in areas of aversive interoceptive processing,
including the insular cortex, but not in areas related to reinforcement, reward
processing or impulsiveness. Our findings suggest that the cortical neuroimmune
regulator TANK is associated with enhanced aversive emotional processing that
better protects from the establishment of alcohol drinking behavior.