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Cereb Cortex. 2019 Apr 1;29(4):1736-1751. doi: 10.1093/cercor/bhy341.

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

Author information

1
Section of Addiction Medicine, Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, Erlangen, Germany.
2
Centre for Population Neuroscience and Stratified Medicine (PONS) and MRC-SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College De Crespigny Park, London, UK.
3
Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina, Chapel Hill NC, USA.
4
The Framingham Heart Study, 73 Mt Wayte Ave, Framingham MA, USA.
5
The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda MD, USA.
6
Boston University School of Public Health, 715 Albany St, Boston MA, USA.
7
Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
8
Institute for Biochemistry and Molecular Medicine, Friedrich-Alexander-University Erlangen-Nuremberg, Fahrstrasse 17, Erlangen, Germany.
9
Laboratory of Host Defense, World Premier International Immunology Frontiern Research Center, Research Institute for Microbial Diseases, Osaka University, 1-1 Yamadaoka, Suita, Osaka, Osaka, Japan.
10
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, Mannheim, Germany.
11
Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, James's Street, Dublin, Ireland.
12
University Medical Centre Hamburg-Eppendorf, House W34, 3.OG, Martinistr. 52, Hamburg, Germany.
13
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, Mannheim, Germany.
14
Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany.
15
NeuroSpin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France.
16
Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA.
17
Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, UK.
18
Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany.
19
Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany [ Physikalisch-Technische Bundesanstalt (PTB), Abbestr. 2-12, Berlin, Germany].
20
Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sud-University Paris Saclay, DIGITEO Labs, Rue Noetzlin, Gif sur Yvette, France.
21
Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sud-Paris Saclay, University Paris Descartes; and AP-HP, Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, Paris, France.
22
Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sud-University Paris Saclay, DIGITEO Labs, Gif sur Yvette; and Psychiatry Department, Orsay Hospital, Orsay, France.
23
Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris-Sud Medical School, France.
24
Rotman Research Institute, Baycrest and Departments of Psychology and Psychiatry, University of Toronto, 3560 Bathurst Street, Toronto, Ontario, Canada.
25
Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, von-Siebold-Str. 5, Göttingen, Germany.
26
Clinic for Child and Adolescent Psychiatry, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria.
27
Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Chemnitzer Str. 46a01187 Dresden, Germany.
28
School of Psychology and Global Brain Health Institute, Aras an Phiarsaigh Trinity College Dublin, Dublin, Ireland.
29
Division of Biological Research on Drug Dependence, Department of Pharmaceutical, Biosciences, Uppsala University, Husargatan 3, Uppsala, Sweden.
30
Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, P.R. China.
31
Department of Anaesthesiology and Intensive Care Medicine, University of Leipzig, Liebigstrasse 20, Leipzig, Germany.

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.

KEYWORDS:

NF-κB; TANK; alcohol; anxiety; drinking; insular cortex

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