Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes.
Delineating the molecular basis of individual differences in the stress response is critical to understanding the pathophysiology and treatment of posttraumatic stress disorder (PTSD). In this study, 7 d after predator-scent-stress (PSS) exposure, male and female rats were classified into vulnerable (i.e., "PTSD-like") and resilient (i.e., minimally affected) phenotypes on the basis of their performance on a variety of behavioral measures. Genome-wide expression profiling in blood and two limbic brain regions (amygdala and hippocampus), followed by quantitative PCR validation, was performed in these two groups of animals, as well as in an unexposed control group. Differentially expressed genes were identified in blood and brain associated with PSS-exposure and with distinct behavioral profiles postexposure. There was a small but significant between-tissue overlap (4-21%) for the genes associated with exposure-related individual differences, indicating convergent gene expression in both sexes. To uncover convergent signaling pathways across tissue and sex, upstream activated/deactivated transcription factors were first predicted for each tissue and then the respective pathways were identified. Glucocorticoid receptor (GR) signaling was the only convergent pathway associated with individual differences when using the most stringent statistical threshold. Corticosterone treatment 1 h after PSS-exposure prevented anxiety and hyperarousal 7 d later in both sexes, confirming the GR involvement in the PSS behavioral response. In conclusion, genes and pathways associated with extreme differences in the traumatic stress behavioral response can be distinguished from those associated with trauma exposure. Blood-based biomarkers can predict aspects of brain signaling. GR signaling is a convergent signaling pathway, associated with trauma-related individual differences in both sexes.
['Daskalakis|Nikolaos P|NP|http://orcid.org/0000-0003-1660-9112', 'Cohen|Hagit|H|', 'Cai|Guiqing|G|', 'Buxbaum|Joseph D|JD|', 'Yehuda|Rachel|R|']
D000679:Amygdala D000818:Animals D001522:Behavior, Animal D001921:Brain D003345:Corticosterone D005260:Female D020869:Gene Expression Profiling D053263:Gene Regulatory Networks D006624:Hippocampus D008297:Male D011235:Predatory Behavior D017207:Rats, Sprague-Dawley D011965:Receptors, Glucocorticoid D012727:Sex Characteristics D015398:Signal Transduction D013313:Stress Disorders, Post-Traumatic
NR3C1 predator stress preventive treatment psychiatry transcription regulation