The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking: A Translational Study

Müller CP, Chu C, Qin L, Liu C, Xu B, Gao H, Ruggeri B, Hieber S, Schneider J, Jia T, Tay N, Akira S, Satoh T, Banaschewski T, Bokde AL, Bromberg U, Büchel C, Quinlan EB, Flor H, Frouin V, Garavan H, Gowland P, Heinz A, Ittermann B, Martinot JL, Martinot MLP, Artiges E, Lemaitre H, Nees F, Papadopoulos Orfanos D, Paus T, Poustka L, Millenet S, Fröhner JH, Smolka MN, Walter H, Whelan R, Bakalkin G, Liu Y, Desrivières S, Elliott P, Eulenburg V, Levy D, Crews F, Schumann G (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Book Volume: 29

Pages Range: 1736-1751

Journal Issue: 4

DOI: 10.1093/cercor/bhy341

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-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.

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Additional Organisation(s)

Involved external institutions

Medical Research Council United Kingdom (GB) National Heart, Lung, and Blood Institute (NHLBI) United States (USA) (US) Osaka University / 大阪大学 Japan (JP) Duke-NUS Medical School / 杜克—国大医学研究生院 Singapore (SG) University of Vermont United States (USA) (US) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) NeuroCure Cluster of Excellence at the Charité Germany (DE) Universität Mannheim Germany (DE) University of Nottingham United Kingdom (GB) Technische Universität Dresden Germany (DE) École Polytechnique - Université Paris-Saclay France (FR) Universitätsklinikum Göttingen Germany (DE) University of North Carolina at Chapel Hill United States (USA) (US) Fudan University / 复旦大学 China (CN) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) France (FR) Physikalisch-Technische Bundesanstalt (PTB) Germany (DE) Uppsala University Sweden (SE) University of Paris 11 - Paris-Sud / Université Paris XI Paris-Sud France (FR) Northern Ontario School of Medicine / École de médecine du Nord de l'Ontario Canada (CA) Trinity College Dublin Ireland (IE) Commissariat à l'énergie atomique France (FR)

How to cite

APA:

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

MLA:

Müller, Christian P., et al. "The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking: A Translational Study." Cerebral Cortex 29.4 (2019): 1736-1751.

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