Brain Region-Specific Gene Expression Changes Following Social Isolation, Oxytocin Treatment, and Acute Stress, in Prairie Voles (Microtus ochrogaster)

Abstract

Social isolation is a biological stressor that is associated with the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and increased risk for mental health disorders. While oxytocin has been identified as a protective factor against the physiological and behavioral consequences of isolation, the brain region-specific transcriptional mechanisms underlying these effects remain unclear. This thesis characterizes the effects of chronic social isolation and acute stress on gene expression across five brain regions in female sibling prairie voles (Microtus ochrogaster). Female sibling prairie voles were assigned to four groups: paired-vehicle (Pv), paired-oxytocin (Po), isolated-vehicle (Iv), and isolated-oxytocin (Io). After a 42-day chronic treatment period, prairie voles underwent a resident-intruder (R-I) test to simulate acute stress. Transcriptomic analysis using RNA sequencing was performed on the hippocampus (HIPP), paraventricular nucleus (PVN), amygdala (AMY), frontal cortex (FC), and bed nucleus of the stria terminalis (BNST). Differential gene expression analysis revealed that there was a lot of region specificity. The HIPP was the most transcriptionally responsive region, with 82 differentially expressed genes between Pv and Iv groups of prairie voles. Functional annotation of these hippocampal genes identified pathways related to neuronal signaling, synaptic function, and oxidative stress response. In comparison, the PVN showed minimal changes upon isolation, with only one gene meeting the predetermined thresholds, while AMY, FC, and BNST showed no detectable transcriptional differences across any comparisons. Although gene expression changes were seen between Pv and Iv groups, oxytocin treatment prevented significant transcriptional changes when compared directly to isolated prairie voles in the comparison Iv vs. Io groups. These findings suggest that the effects of social isolation on gene expression in the brain are primarily being driven by the social environment rather than widespread transcriptional regulation from oxytocin