Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Kondashevskaya MV

PROVIDER: S-EPMC10455150 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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

Kondashevskaya Marina V MV Mikhaleva Lyudmila M LM Artem'yeva Kseniya A KA Aleksankina Valentina V VV Areshidze David A DA Kozlova Maria A MA Pashkov Anton A AA Manukhina Eugenia B EB Downey H Fred HF Tseilikman Olga B OB Yegorov Oleg N ON Zhukov Maxim S MS Fedotova Julia O JO Karpenko Marina N MN Tseilikman Vadim E VE

International journal of molecular sciences 20230821 16

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 pred ...[more]

PMID: 37629192

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Project description:IntroductionThe liver receives gut-derived endotoxin via the portal vein, clearing it before it enters systemic circulation. Hemodialysis negatively impacts the perfusion and function of multiple organs systems. Dialysate cooling reduces hemodialysis-induced circulatory stress and protects organs from ischemic injury. This study examined how hemodialysis disrupts liver hemodynamics and function, its effect on endotoxemia, and the potential protective effect of dialysate cooling.MethodsFifteen patients were randomized to receive either standard (36.5°C dialysate temperature) or cooled (35.0°C) hemodialysis first in a two-visit crossover trial. We applied computed tomography (CT) liver perfusion imaging to patients before, 3 hours into and after each hemodialysis session. We measured hepatic perfusion and perfusion heterogeneity. Hepatic function was measured by indocyanine green (ICG) clearance. Endotoxin levels in blood throughout dialysis were also measured.ResultsDuring hemodialysis, overall liver perfusion did not significantly change, but portal vein perfusion trended towards increasing (P = 0.14) and perfusion heterogeneity significantly increased (P = 0.038). In addition, ICG clearance decreased significantly during hemodialysis (P = 0.016), and endotoxin levels trended towards increasing during hemodialysis (P = 0.15) and increased significantly after hemodialysis (P = 0.037). Applying dialysate cooling trended towards abrogating these changes but did not reach statistical significance compared to standard hemodialysis.ConclusionHemodialysis redistributes liver perfusion, attenuates hepatic function, and results in endotoxemia. Higher endotoxin levels in end-stage renal disease (ESRD) patients may result from the combination of decreased hepatic clearance function and increasing fraction of liver perfusion coming from toxin-laden portal vein during hemodialysis. The protective potential of dialysate cooling should be explored further in future research studies.

Project description:IntroductionBoth trauma exposure and post-traumatic stress disorder (PTSD) are associated with increased risk of cardiovascular disease (CVD), the leading cause of death in the USA. Endothelial dysfunction, a modifiable, early marker of CVD risk, may represent a physiological mechanism underlying this association. This mechanism-focused cohort study aims to investigate the relationship between PTSD (both in terms of diagnosis and underlying symptom dimensions) and endothelial dysfunction in a diverse, community-based sample of adult men and women.Methods and analysisUsing a cohort design, 160 trauma-exposed participants without a history of CVD are designated to the PTSD group (n=80) or trauma-exposed matched control group (n=80) after a baseline diagnostic interview assessment. Participants in the PTSD group have a current (past month) diagnosis of PTSD, whereas those in the control group have a history of trauma but no current or past psychiatric diagnoses. Endothelial dysfunction is assessed via flow-mediated vasodilation of the brachial artery and circulating levels of endothelial cell-derived microparticles. Two higher order symptom dimensions of PTSD-fear and dysphoria-are measured objectively with a fear conditioning paradigm and attention allocation task, respectively. Autonomic imbalance, inflammation, and oxidative stress are additionally assessed and will be examined as potential pathway variables linking PTSD and its dimensions with endothelial dysfunction. Participants are invited to return for a 2-year follow-up visit to reassess PTSD and its dimensions and endothelial dysfunction in order to investigate longitudinal associations.Ethics and disseminationThis study is conducted in compliance with the Helsinki Declaration and University of California, Los Angeles Institutional Review Board. The results of this study will be disseminated via articles in peer-reviewed journals and presentations at academic conferences and to community partners.Trial registration numberNCT03778307; pre-results.

Dataset Information

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

Publications

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

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