TY - JOUR

T1 - Unveiling the Link: Exploring Mitochondrial Dysfunction as a Probable Mechanism of Hepatic Damage in Post-Traumatic Stress Syndrome

AU - Kondashevskaya, Marina V

AU - Mikhaleva, Lyudmila M

AU - Artem'yeva, Kseniya A

AU - Aleksankina, Valentina V

AU - Areshidze, David A

AU - Kozlova, Maria A

AU - Pashkov, Anton A

AU - Manukhina, Eugenia B

AU - Downey, H Fred

AU - Tseilikman, Olga B

AU - Yegorov, Oleg N

AU - Zhukov, Maxim S

AU - Fedotova, Julia O

AU - Karpenko, Marina N

AU - Tseilikman, Vadim E

N1 - This work was performed as part of the basic portion of a State Assignment to the A.P. Avtsyn Research Institute of Human Morphology of B.V. Petrovsky National Research Center of Surgery # 122030200535-1 and as part of the State Assignment to the Institute of General Pathology and Pathophysiology # FGFU-2022-0011. Separately, the research of oxidative stress was supported by Russian Scientific Foundation, (Regional grant, Chelyabinsk Region) # 23-15-20040.

PY - 2023/8/21

Y1 - 2023/8/21

N2 - 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.

AB - 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.

KW - Animals

KW - Rats

KW - Stress Disorders, Post-Traumatic

KW - Anxiety Disorders

KW - Anxiety/etiology

KW - Liver

KW - Mitochondria

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85168749258&origin=inward&txGid=223a58a74e0f0bc4e4b5d5c840428c81

U2 - 10.3390/ijms241613012

DO - 10.3390/ijms241613012

M3 - Article

C2 - 37629192

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 16

M1 - 13012

ER -