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

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
doi: 10.1371/journal.pgen.1008358


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:

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


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