The cortical neuroimmune regulator TANK affects emotional processing and enhances alcohol drinking: a translational study

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; Paillère Martinot, Marie-Laure; Artiges, Eric; Lemaitre, Herve; Nees, Frauke; Papadopoulos Orfanos, Dimitri; Paus, Tomas; Poustka, Luise; Millenet, Sabina; Fröhner, Juliane H.; Smolka, Michael N.; Walter, Henrik; Whelan, Robert; Bakalkin, Georgy; Liu, Yun; Desrivieres, Sylvane; Elliott, Paul; Eulenburg, Volker; Levy, Daniel; Crews, Fulton; Schumann, Gunter

Abstract

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-kappaB activator’ (TANK) affects alcohol drinking behaviour. 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=1.16x10-19) and regional methylation (p=5.90x10-25). A tank knock out mouse model suggests a role of TANK in alcohol drinking, anxiety-related behaviour, as well as alcohol exposure induced activation of insular cortex NF-kappaB. Functional and structural neuroimaging studies among up to 1,896 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 behaviour.

Citation

Müller, C. P., Chu, C., Qin, L., Liu, C., Xu, B., Gao, H., …Schumann, G. (2019). The cortical neuroimmune regulator TANK affects emotional processing and enhances alcohol drinking: a translational study. Cerebral Cortex, 29(4), 1736–1751. https://doi.org/10.1093/cercor/bhy341

• Journal Article Type: Article
• Acceptance Date: Dec 18, 2018
• Online Publication Date: Feb 4, 2019
• Publication Date: 2019-04
• Deposit Date: Dec 19, 2018
• Publicly Available Date: Dec 19, 2018
• Journal: Cerebral Cortex
• Print ISSN: 1047-3211
• Electronic ISSN: 1460-2199
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 29
• Issue: 4
• Pages: 1736–1751
• DOI: https://doi.org/10.1093/cercor/bhy341
• Keywords: Cognitive Neuroscience; Cellular and Molecular Neuroscience
• Public URL: https://nottingham-repository.worktribe.com/output/1426005
• Publisher URL: https://academic.oup.com/cercor/advance-article/doi/10.1093/cercor/bhy341/5306317