Event:

Anxiety disorders are complex diseases with largely unknown etiology. We have taken a cross-species approach to identify genes that regulate anxiety-like behavior using inbred mouse strains that differ in their innate anxiety levels. To identify genes that regulate anxiety we have carried out RNAseq and miRNAseq in the frontal cortex and hippocampus of six inbred strains. We then correlated the gene expression levels with their levels of anxiety-like behavior (measured by the open field and light dark box tests) to identify gene networks that putatively regulate anxiety. In the hippocampus, the differentially expressed genes were enriched in the vesicle mediated transport, mitotic nuclear division, and lipid metabolism Gene Ontology categories. In the frontal cortex, we observed enrichment in the cell division, vesicle mediated transport, and lipid metabolism categories.

In addition to innate anxiety, we have investigated the effect of genetic background on stress-induced anxiety. We use the chronic social defeat, a well-characterized model for psychosocial stress in mice, and carried out RNAseq and miRNAseq from medial prefrontal cortex and ventral hippocampus in C57BL/6 (a non-anxious strain) and DBA/2 (an anxious strain) mice. Intriguingly, the behavioral results and differential expression analysis showed distinct response to chronic psychosocial stress in the two strains implying that genetic background has a large effect on stress-induced behavior and brain transcriptional response. Our current aim is to determine whether the pathways identified using mouse models are involved in the etiology of human anxiety disorders.