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

English version

Autoři: Zuzanna Misiewicz ^aff001; Stella Iurato ^aff002; Natalia Kulesskaya ^aff001; Laura Salminen ^aff001; Luis Rodrigues ^aff002; Giuseppina Maccarrone ^aff002; Jade Martins ^aff002; Darina Czamara ^aff002; Mikaela A. Laine ^aff001; Ewa Sokolowska ^aff001; Kalevi Trontti ^aff001; Christiane Rewerts ^aff002; Bozidar Novak ^aff002; Naama Volk ^aff004; Dong Ik Park ^aff002; Eija Jokitalo ^aff005; Lars Paulin ^aff006; Petri Auvinen ^aff006; Vootele Voikar ^aff007; Alon Chen ^aff004; Angelika Erhardt ^aff002; Christoph W. Turck ^aff002; Iiris Hovatta ^aff001
Působiště autorů: Molecular and Integrative Biosciences Research Program, University of Helsinki, Helsinki, Finland ^aff001; Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany ^aff002; Department of Psychology and Logopedics, Medicum, University of Helsinki, Helsinki, Finland ^aff003; Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel ^aff004; Electron Microscopy Unit, Institute of Biotechnology, University of Helsinki, Helsinki, Finland ^aff005; Institute of Biotechnology, University of Helsinki, Helsinki, Finland ^aff006; Neuroscience Center, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland ^aff007; Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany ^aff008
Vyšlo v časopise: Multi-omics analysis identifies mitochondrial pathways associated with anxiety-related behavior. PLoS Genet 15(9): e32767. doi:10.1371/journal.pgen.1008358
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1008358

Souhrn

Stressful life events are major environmental risk factors for anxiety disorders, although not all individuals exposed to stress develop clinical anxiety. The molecular mechanisms underlying the influence of environmental effects on anxiety are largely unknown. To identify biological pathways mediating stress-related anxiety and resilience to it, we used the chronic social defeat stress (CSDS) paradigm in male mice of two inbred strains, C57BL/6NCrl (B6) and DBA/2NCrl (D2), that differ in their susceptibility to stress. Using a multi-omics approach, we identified differential mRNA, miRNA and protein expression changes in the bed nucleus of the stria terminalis (BNST) and blood cells after chronic stress. Integrative gene set enrichment analysis revealed enrichment of mitochondrial-related genes in the BNST and blood of stressed mice. To translate these results to human anxiety, we investigated blood gene expression changes associated with exposure-induced panic attacks. Remarkably, we found reduced expression of mitochondrial-related genes in D2 stress-susceptible mice and in exposure-induced panic attacks in humans, but increased expression of these genes in B6 stress-susceptible mice. Moreover, stress-susceptible vs. stress-resilient B6 mice displayed more mitochondrial cross-sections in the post-synaptic compartment after CSDS. Our findings demonstrate mitochondrial-related alterations in gene expression as an evolutionarily conserved response in stress-related behaviors and validate the use of cross-species approaches in investigating the biological mechanisms underlying anxiety disorders.

Klíčová slova:

Gene expression – Blood cells – Psychological stress – Mice – MicroRNAs – Mitochondria – Transcriptome analysis – Panic disorder

Zdroje

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