Multi-omics analysis identifies mitochondrial pathways associated with anxiety-related behavior

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Misiewicz , Z , Iurato , S , Kulesskaya , N , Salminen , L , Rodrigues , L , Maccarrone , G , Martins , J , Czamara , D , Laine , M A , Sokolowska , E , Trontti , K , Rewerts , C , Novak , B , Volk , N , Park , D I , Jokitalo , E , Paulin , L , Auvinen , P , Voikar , V , Chen , A , Erhardt , A , Turck , C W & Hovatta , I 2019 , ' Multi-omics analysis identifies mitochondrial pathways associated with anxiety-related behavior ' , PLoS Genetics , vol. 15 , no. 9 , 1008358 , pp. e1008358 . https://doi.org/10.1371/journal.pgen.1008358

Title: Multi-omics analysis identifies mitochondrial pathways associated with anxiety-related behavior
Author: Misiewicz, Zuzanna; Iurato, Stella; Kulesskaya, Natalia; Salminen, Laura; Rodrigues, Luis; Maccarrone, Giuseppina; Martins, Jade; Czamara, Darina; Laine, Mikaela A.; Sokolowska, Ewa; Trontti, Kalevi; Rewerts, Christiane; Novak, Bozidar; Volk, Naama; Park, Dong Ik; Jokitalo, Eija; Paulin, Lars; Auvinen, Petri; Voikar, Vootele; Chen, Alon; Erhardt, Angelika; Turck, Christoph W.; Hovatta, Iiris
Contributor: University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, SLEEPWELL Research Program
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, SLEEPWELL Research Program
University of Helsinki, Electron Microscopy
University of Helsinki, Institute of Biotechnology
University of Helsinki, DNA Sequencing and Genomics
University of Helsinki, Neuroscience Center
University of Helsinki, Department of Psychology and Logopedics
Date: 2019-09-26
Language: eng
Number of pages: 33
Belongs to series: PLoS Genetics
ISSN: 1553-7390
URI: http://hdl.handle.net/10138/306797
Abstract: Author summary Genetic and environmental factors contribute to the etiology of psychiatric diseases but the underlying mechanisms are poorly understood. Chronic psychosocial stress is a well-known risk factor for anxiety disorders. To identify biological pathways involved in psychosocial stress-induced anxiety and resilience to it, we used a well-characterized mouse model of chronic social defeat stress (CSDS) in two inbred mouse strains, C57BL/6NCrl (B6) and DBA/2NCrl (D2), which differ in their susceptibility to stress. We focused on the bed nucleus of the stria terminalis, a key brain region behind stress-response and anxiety, and carried out genome-wide analysis of mRNA, and miRNA expression, and protein abundance. Bioinformatic integration of these data supported differences in mitochondrial pathways as a major stress response. To translate these findings to human anxiety, we investigated blood cell gene expression in mice and in panic disorder patients exposed to fearful situations and experiencing panic attacks. Concurring with our brain findings, expression of mitochondrial pathways was also affected in mouse and human blood cells, suggesting that the observed stress response mechanisms are evolutionarily conserved. Therefore, chronic stress may critically affect cellular energy metabolism, a finding that may offer new targets for therapeutic interventions of stress-related diseases.
Subject: 1184 Genetics, developmental biology, physiology
1182 Biochemistry, cell and molecular biology
SOCIAL DEFEAT STRESS
FORCED SWIMMING TEST
CHRONIC MILD STRESS
GENE-EXPRESSION
BED NUCLEUS
PSYCHOLOGICAL STRESS
STATISTICAL-ANALYSIS
STRAIN DIFFERENCES
STRIA TERMINALIS
RISK-FACTORS
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