The cortical neuroimmune regulator TANK affects emotional processing and enhances alcohol drinking: a translational study
File(s)
Published version
Author(s)
Type
Journal Article
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.
Date Issued
2019-02-04
Date Acceptance
2018-12-19
Citation
Cerebral Cortex, 2019, 29 (4), pp.1736-1751
ISSN
1047-3211
Publisher
Oxford University Press (OUP)
Start Page
1736
End Page
1751
Journal / Book Title
Cerebral Cortex
Volume
29
Issue
4
Copyright Statement
© The Author(s) 2019. Published by Oxford University Press.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properlycited.For commercial re-use, please contactjournals.permissions@oup.com
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30721969
PII: 5306317
Grant Number
MR/L01341X/1
RTJ964197401
Subjects
1109 Neurosciences
1702 Cognitive Science
Experimental Psychology
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2019-02-04