Unveiling the Link: Exploring Mitochondrial Dysfunction as a Probable Mechanism of Hepatic Damage in Post-Traumatic Stress Syndrome.

PTSD is associated with disturbed hepatic morphology and metabolism. Neuronal mitochondrial dysfunction is considered a subcellular determinant of PTSD, but a link between hepatic mitochondrial dysfunction and hepatic damage in PTSD has not been demonstrated. Thus, the effects of experimental PTSD on the livers of high anxiety (HA) and low anxiety (LA) rats were compared, and mitochondrial determinants underlying the difference in their hepatic damage were investigated. Rats were exposed to predator stress for 10 days. Then, 14 days post-stress, the rats were evaluated with an elevated plus maze and assigned to HA and LA groups according to their anxiety index. Experimental PTSD caused dystrophic changes in hepatocytes of HA rats and hepatocellular damage evident by increased plasma ALT and AST activities. Mitochondrial dysfunction was evident as a predominance of small-size mitochondria in HA rats, which was positively correlated with anxiety index, activities of plasma transaminases, hepatic lipids, and negatively correlated with hepatic glycogen. In contrast, LA rats had a predominance of medium-sized mitochondria. Thus, we show links between mitochondrial dysfunction, hepatic damage, and heightened anxiety in PTSD rats. These results will provide a foundation for future research on the role of hepatic dysfunction in PTSD pathogenesis.

Cerebral Blood Flow in Predator Stress-Resilient and -Susceptible Rats and Mechanisms of Resilience.

Stress-induced conditions are associated with impaired cerebral blood flow (CBF) and increased risk of dementia and stroke. However, these conditions do not develop in resilient humans and animals. Here the effects of predator stress (PS, cat urine scent, ten days) on CBF and mechanisms of CBF regulation were compared in PS-susceptible (PSs) and PS-resilient (PSr) rats. Fourteen days post-stress, the rats were segregated into PSs and PSr groups based on a behavior-related anxiety index (AI). CBF and its endothelium-dependent changes were measured in the parietal cortex by laser Doppler flowmetry. The major findings are: (1) PS susceptibility was associated with reduced basal CBF and endothelial dysfunction. In PSr rats, the basal CBF was higher, and endothelial dysfunction was attenuated. (2) CBF was inversely correlated with the AI of PS-exposed rats. (3) Endothelial dysfunction was associated with a decrease in eNOS mRNA in PSs rats compared to the PSr and control rats. (4) Brain dopamine was reduced in PSs rats and increased in PSr rats. (5) Plasma corticosterone of PSs was reduced compared to PSr and control rats. (6) A hypercoagulation state was present in PSs rats but not in PSr rats. Thus, potential stress resilience mechanisms that are protective for CBF were identified.