Molecular Mechanisms Underlying Individual Differences in Response to Stress in a Previously Validated Animal Model of PTSD.

摘要

It is unclear why some individuals develop PTSD while others do not. Pre-existing biological differences among individuals may predispose some and not others to develop PTSD. We are seeking to identify such biological differences using an existing rat model for PTSD where exposure to a predator stress scent (PSS) results in extreme behavioral responses for 25% of animals (EBR) thought to be analogous to PTSD, while 25% of the animals show minimal behavioral responses (MBR). Our objectives for Experiment 1 were to identify genes showing altered mRNA expression in blood and brain areas implicated in PTSD that relate to individual differences in fear reactivity. Our goal in Experiment 2 was to examine the prophylactic effects of exogenous glucocorticoids on the behavioral and gene expression effects of stress exposure. We have completed the behavioral work for Exp.1 and Exp.2 and successfully produced rats with the behavioral phenotypes that were required for our gene expression aims. Gene expression profiling of Exp.1 has been completed on all brain samples and on a portion of the blood. Among others, differential expression of genes (e.g. FKBP5) regulated by the glucocorticoid- receptor (GR) underlies the behavioral differences. The small overlap in gene expression between different tissue and gender demonstrated the existence of distinct tissue specific susceptibility pathways in males and females. Gene expression profiling of the samples of Exp.2 is ongoing.