Universität zu Köln

Velo Escarcena, Laura, Neufeld, Margarita, Rietschel, Marcella, Spanagel, Rainer and Scholz, Henrike (2021). ERR and dPECR Suggest a Link Between Neuroprotection and the Regulation of Ethanol Consumption Preference. Front. Psychiatry, 12. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-0640

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Abstract

Reconsumption of ethanol after withdrawal is a hallmark for relapse in recovering patients with alcohol use disorders. We show that the preference of Drosophila melanogaster to reconsume ethanol after abstinence shares mechanistic similarities to human behavior by feeding the antirelapse drug acamprosate to flies and reducing the ethanol consumption preference. The Drosophila cellular stress mutant hangover also reduced ethanol consumption preference. Together with the observation that an increasing number of candidate genes identified in a genome-wide association study on alcohol use disorders are involved in the regulation of cellular stress, the results suggest that cellular stress mechanisms might regulate the level of ethanol reconsumption after abstinence. To address this, we analyzed mutants of candidate genes involved in the regulation of cellular stress for their ethanol consumption level after abstinence and cellular stress response to free radicals. Since hangover encodes a nuclear RNA-binding protein that regulates transcript levels, we analyzed the interactions of candidate genes on transcript and protein level. The behavioral analysis of the mutants, the analysis of transcript levels, and protein interactions suggested that at least two mechanisms regulate ethanol consumption preference after abstinence-a nuclear estrogen-related receptor-hangover-dependent complex and peroxisomal trans-2-enoyl-CoA reductase (dPECR)-dependent component in peroxisomes. The loss of estrogen-like receptor and dPECR in neurons share a protective function against oxidative stress, suggesting that the neuroprotective function of genes might be a predictor for genes involved in the regulation of ethanol reconsumption after abstinence.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Velo Escarcena, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Neufeld, Margarita UNSPECIFIED UNSPECIFIED UNSPECIFIED Rietschel, Marcella UNSPECIFIED UNSPECIFIED UNSPECIFIED Spanagel, Rainer UNSPECIFIED UNSPECIFIED UNSPECIFIED Scholz, Henrike UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-575247
DOI:	10.3389/fpsyt.2021.655816
Journal or Publication Title:	Front. Psychiatry
Volume:	12
Date:	2021
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-0640
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Psychiatry Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57524