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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

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Authors

Christian P. Müller

Congying Chu

Liya Qin

Chunyu Liu

Bing Xu

He Gao

Barbara Ruggeri

Saskia Hieber

Julia Schneider

Tianye Jia

Nicole Tay

Shizuo Akira

Takashi Satoh

Tobias Banaschewski

Arun L.W. Bokde

Uli Bromberg

Christian Büchel

Erin Burke Quinlan

Herta Flor

Vincent Frouin

Hugh Garavan

Andreas Heinz

Bernd Ittermann

Jean-Luc Martinot

Marie-Laure Paillère Martinot

Eric Artiges

Herve Lemaitre

Frauke Nees

Dimitri Papadopoulos Orfanos

Tomas Paus

Luise Poustka

Sabina Millenet

Juliane H. Fröhner

Michael N. Smolka

Henrik Walter

Robert Whelan

Georgy Bakalkin

Yun Liu

Sylvane Desrivieres

Paul Elliott

Volker Eulenburg

Daniel Levy

Fulton Crews

Gunter Schumann



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