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The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking: A Translational Study
Friedrich Alexander Univ Erlangen Nuremberg, Univ Clin, Dept Psychiat & Psychotherapy, Sect Addict Med, Schwabachanlage 6, D-91054 Erlangen, Germany.
Kings Coll London, Inst Psychiat Psychol & Neurosci, Ctr Populat Neurosci & Stratified Med PONS, De Crespigny Pk, London SE5 8AF, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, De Crespigny Pk, London SE5 8AF, England.
Univ N Carolina, Sch Med, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA.
Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA;NHLBI, Populat Sci Branch, Div Intramural Res, Bethesda, MD 20824 USA;Boston Univ, Sch Publ Hlth, 715 Albany St, Boston, MA 02118 USA.
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2019 (English)In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 29, no 4, p. 1736-1751Article in journal (Refereed) Published
Abstract [en]

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-kappa B 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 x 10(-19)) and regional methylation (P = 5.90 x 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-kappa B. 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.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS INC , 2019. Vol. 29, no 4, p. 1736-1751
Keywords [en]
alcohol, anxiety, drinking, insular cortex, NF-kappa B, TANK
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-393754DOI: 10.1093/cercor/bhy341ISI: 000482180900035PubMedID: 30721969OAI: oai:DiVA.org:uu-393754DiVA, id: diva2:1362378
Funder
EU, Horizon 2020, 695313EU, FP7, Seventh Framework Programme, 602450EU, FP7, Seventh Framework Programme, 603016Swedish Research Council FormasGerman Research Foundation (DFG), SM 80/7-1German Research Foundation (DFG), SM 80/7-2German Research Foundation (DFG), SFB 940/1Available from: 2019-10-18 Created: 2019-10-18 Last updated: 2019-10-18Bibliographically approved

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