Phenotypically Determined Liver Dysfunction in a Wistar Rat Model of Post-Traumatic Stress Disorder.

The extraordinary situation of the 2019-2022 pandemic caused a dramatic jump in the incidence of post-traumatic stress disorder (PTSD). PTSD is currently regarded not only as a neuropsychiatric disorder, but also as a comorbidity accompanied by cardiovascular diseases, circulatory disorders, liver dysfunction, etc. The relationship between behavioral disorders and the degree of morphofunctional changes in the liver remains obscure. In this study, PTSD was modeled in sexually mature male Wistar rats using predatory stress induced by a prey's fear for a predator. Testing in an elevated plus maze allowed the rat population to be divided into animals with low-anxiety (LAP) and high-anxiety (HAP) phenotypes. It was found that morphofunctional analysis of the liver, in contrast to its biochemical profiling, provides a clearer evidence that predatory stress induces liver dysfunction in rats of both phenotypes. This may indicate a decrease in the range of compensatory adaptive reactions in stressed animals. However, in HAP rats, the level of morphofunctional abnormalities in the mechanisms responsible for carbohydrate-fat, water-electrolyte and protein metabolism in the liver testified the prenosological state of the organ, while further functional loading and resulting tension of the regulatory systems could lead to homeostatic downregulation. Meanwhile, the liver of LAP animals was only characterized by insignificant diffuse changes. Thus, we demonstrate here a link between behavioral changes and the degree of morphofunctional transformation of the liver.

New Morphofunctional Criteria for Resistance Profile in Post-Traumatic Stress Disorder Models as Adrenal Dysfunction Trigger.

For the first time in modeling posttraumatic stress disorder (PTSD), we have described the morphofunctional state of adrenal glands in Wistar rats resistant and sensitive to predator stress (rodent fear of the predator). Despite the evident signs of adrenal dysfunction in both phenotypes, we have discovered the thickening of undifferentiated cell zone and high indices of functional activity of stem cells in resistant animals, suggesting ample adaptation. The most important data demonstrate the direct relationship between the reduction of corticosterone and testosterone levels and adrenal dysfunction in PTSD models. The study results allow considering the adrenal stem cells as potential therapeutic targets.