Individual variability of microRNAs in the prefrontal cortex of an animal model of post-traumatic stress disorder

When confronting with stress, most individuals stay resilient while a minor population develops anxiety disorders like post-traumatic stress disorder (PTSD). The etiology of such divergent behavioral response to stress remains unknown. Here, we sort to examine the expression of miRNAs, the key modulators of gene expression, in the mouse prefrontal cortex of the predator-exposure model of PTSD, with the aim to identify miRNAs that are potentially involved in individual variability in stress response. We noticed that about 33% and 14% of the stress-exposed and unexposed animals developed long-term anxiety, respectively. Based on their anxiety, they were further grouped as "anxious" (i.e. susceptible) and "non-anxious" (i.e. resilient) animals. From the microarray and RT-qPCR analysis conducted in the mRNA pool of these groups, we identified many miRNAs that were specifically regulated in susceptible and resilient groups, independent of their previous stress exposure. We compared all our groups to stress-unexposed resilient animals as it represented an ideal control. We observed miRNAs like miR-451a and miR-144 to be specifically upregulated in the stress susceptible animals while, miRNAs like miR-132 and miR-9-5p to be upregulated in stress resilient animals. Interestingly, miR-451a and miR-144 along with miR-222 and miR-221 was also found to downregulated in the stress-unexposed susceptible animals. Further, by performing RT-qPCR in individual animal samples, we also confirmed the pool results of miR-451a and miR-144. From our preliminary results, we propose that these miRNAs in prefrontal cortex could have potential role in regulating susceptibility/resilience to stress and could also be possible candidates for PTSD biomarkers in future.