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

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Stressful life events are risk factors for anxiety disorders, but individual responses vary.
• The molecular mechanisms linking environmental stress to anxiety and resilience remain largely unknown.

Purpose of the Study:

• To identify biological pathways mediating stress-related anxiety and resilience.
• To investigate the role of mitochondrial gene expression in anxiety disorders across species.

Main Methods:

• Utilized the chronic social defeat stress (CSDS) paradigm in two mouse strains with differing stress susceptibility (B6 and D2).
• Employed a multi-omics approach (mRNA, miRNA, protein expression) in the bed nucleus of the stria terminalis (BNST) and blood.
• Analyzed blood gene expression in humans experiencing panic attacks.

Main Results:

• Chronic stress induced differential gene expression, particularly involving mitochondrial pathways, in the BNST and blood of mice.
• Mitochondrial gene expression patterns differed based on stress susceptibility: decreased in D2 mice and humans with panic attacks, increased in B6 mice.
• Stress-susceptible B6 mice showed increased mitochondrial cross-sections in neuronal synapses post-stress.

Conclusions:

• Mitochondrial gene expression alterations are an evolutionarily conserved response to stress-related behaviors.
• Cross-species approaches are valuable for understanding the biological underpinnings of anxiety disorders.
• Identified mitochondrial pathways as potential targets for anxiety disorder research.