UROCORTINS AS MODULATORS OF BEHAVIOR, NEUROGENESIS, AND MICROBIOTA IN AN ANIMAL MODEL OF PTSD

Post-traumatic stress disorder (PTSD) induces dysregulation of the hypothalamic–pituitary–adrenal axis, together with alterations in neurogenesis and gut microbiota. Emerging evidence indicates that urocortins (UCNs), members of the corticotropin-releasing factor family, may influence both neurogenesis and gut–brain communication. In this study, we examined the effect of a single intranasal dose of urocortin (UCN2/UCN3; 20 µg/kg) on anxiety-like behavior, hippocampal neurogenesis, and spleen bacterial composition in a single prolonged stress (SPS) animal model of PTSD. Anxiety-like behavior was assessed using the elevated plus maze (EPM) and open field (OF) tests. Neurogenesis in the ventral and dorsal hippocampus (vHip, dHip) was evaluated using proliferation and neuronal differentiation markers, and spleen bacteria by 16S rRNA gene expression. SPS-induced anxiety-like behavior in the OF was suppressed only by UCN3. SPS increased doublecortin mRNA levels in the vHip compared to controls. Both UCN2 and UCN3 suppressed this elevation towards the baseline. Intranasal UCN2 reduced splenic Enterobacteriaceae 16S rRNA levels relative to SPS animals, whereas UCN3 increased total bacteria, Enterococcus, and Lactobacillus 16S rRNA levels in comparison with SPS and/or UCN2 treatment. Our findings suggest that UCN3, in contrast to UCN2, partially mitigates PTSD-induced anxiety in the OF. Both used peptides counteracted SPS-induced neurogenic changes, yet they differed markedly in their impact on spleen microbial composition, with UCN3 displaying a broader immune-behavioral effect and a stronger modulatory impact on the microbiota in the context of PTSD-like pathology.
Supported by VEGA 2/0045/26 and APVV-24-0213.