The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking: A Translational Study.
СтатьяПоддержка NIH: внешняя программаResearch Support, N.I.H., IntramuralПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Müller Christian P, Chu Congying, Qin Liya, Liu Chunyu, Xu Bing, Gao He, Ruggeri Barbara, Hieber Saskia, Schneider Julia, Jia Tianye, Tay Nicole, Akira Shizuo, Satoh Takashi, Banaschewski Tobias, Bokde Arun L W, Bromberg Uli, Büchel Christian, Quinlan Erin Burke, Flor Herta, Frouin Vincent, Garavan Hugh, Gowland Penny, Heinz Andreas, Ittermann Bernd, Martinot Jean-Luc, Martinot Marie-Laure Paillère, Artiges Eric, Lemaitre Herve, Nees Frauke, Papadopoulos Orfanos Dimitri, Paus Tomáš, Poustka Luise, Millenet Sabina, Fröhner Juliane H, Smolka Michael N, Walter Henrik, Whelan Robert, Bakalkin Georgy, Liu Yun, Desrivières Sylvane, Elliott Paul, Eulenburg Volker, Levy Daniel, Crews Fulton, Schumann Gunter
Аннотация
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.