Individual variability of miRNAs in prefrontal cortex in an animal model of PTSD

Traumatic stress experienced during adulthood can increase the vulnerability in some individuals to develop a long-term anxiety disorder known as post-traumatic stress disorder (PTSD). It is well documented that stress induces plastic changes in the brain differentially between the PTSD susceptible and resilient individuals. But the molecular basis of such differential alterations is still unknown. In this study, we have examined the altered expression of miRNAs, key modulators of gene expression, in the prefrontal cortex in an animal model of PTSD with an aim to identify miRNAs that could form the basis of such susceptibility and resilience. Similar to the individual variability seen in human population in developing PTSD, we witnessed different levels of long-term anxiety in our control and stressed animals. This allowed us to further divide them into "extremely-anxious" and "non-anxious" groups. Our preliminary data from microarray analysis suggests that miR-144, miR-451 and several other miRNAs could have a potential role in the molecular etiology of the differential vulnerability towards long-term anxiety and PTSD in general. In our analysis, the expression of miR-144 and miR-451 were always found to be down-regulated in the non-anxious animals compared to the extremely-anxious animals regardless of the stress exposure. This suggested us the possible role of the respective miRNAs in maintaining stress resilience in these animals. Interestingly, there were several other miRNAs that were specifically up-regulated in condition of extreme anxiety following a traumatic stress exposure emphasizing their possible function in enhancing susceptibility towards anxiety when exposed to a trauma. By performing bioinformatics analysis, we came to know that our potential miRNAs have gene targets, which were predominantly involved in miRNA regulation, apoptosis, neuronal plasticity and development. Ongoing studies in the lab will validate the other miRNAs so as to better understand the molecular mechanism underlying the differential variabilty caused in response to stress.