PROFILING SEX-SPECIFIC GENE/PROTEIN REGULATION FOLLOWING SINGLE PROLONGED STRESS IN SPRAGUE DAWLEY RATS: INSIGHT FROM INFRALIMBIC CORTEX AND BASOLATERAL AMYGDALA TRANSCRIPTOMICS AND PROTEOMICS ANALYSIS

Exposure to severe stress causes physiological and behavioral changes that can increase vulnerability to psychiatric disorders such as post-traumatic stress disorder (PTSD). However, the molecular alterations following severe stress that contribute to this vulnerability are not well understood. We have conducted bulk RNA sequencing and liquid chromatography-mass spectrometry on infralimbic cortex (IL) and basolateral amygdala (BLA) tissue from male and female Sprague Dawley rats exposed to single prolonged stress (SPS) (rodent PTSD model) or control conditions. Differential expression, pathway enrichment, and integrative cross-region analyses are being performed to identify stress- and sex-associated molecular signatures. Initial transcriptomic analyses indicate that extracellular matrix-related pathways are upregulated in the female IL and down-regulated in the female BLA. In contrast, pathways related to G-protein coupled receptors (GPCR) and synaptic signaling are down-regulated in the female IL and upregulated in the female BLA. Male transcriptional profiles differ, with predominant upregulation of pathways related to cell-replication in the IL and relatively limited changes in the BLA. Direct comparisons between female and male IL expression reveal several genes related to GPCR and synaptic signaling that are significantly discordant, showing downregulation in females and upregulation in males. Together, these preliminary findings suggest sex-specific molecular programs following exposure to an acute severe stressor. This work will help elucidate molecular mechanisms underlying stress adaptation across corticolimbic circuits and may inform sex-specific vulnerability and resilience observed in SPS animal models and in humans exposed to traumatic events.