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

Marina V Kondashevskaya; Lyudmila M Mikhaleva; Kseniya A Artem'yeva; Valentina V Aleksankina; David A Areshidze; Maria A Kozlova; Anton A Pashkov; Eugenia B Manukhina; H Fred Downey; Olga B Tseilikman; Oleg N Yegorov; Maxim S Zhukov; Julia O Fedotova; Marina N Karpenko; Vadim E Tseilikman

doi:10.3390/ijms241613012

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

Int J Mol Sci. 2023 Aug 21;24(16):13012. doi: 10.3390/ijms241613012.

Authors

Marina V Kondashevskaya¹, Lyudmila M Mikhaleva¹, Kseniya A Artem'yeva¹, Valentina V Aleksankina¹, David A Areshidze¹, Maria A Kozlova¹, Anton A Pashkov^{2

3}, Eugenia B Manukhina^{4

5}, H Fred Downey⁴, Olga B Tseilikman^{2

6}, Oleg N Yegorov⁶, Maxim S Zhukov¹, Julia O Fedotova⁷, Marina N Karpenko⁸, Vadim E Tseilikman^{2

9}

Affiliations

¹ A.P. Avtsyn Research Institute of Human Morphology, B.V. Petrovsky National Research Center of Surgery, Moscow 119991, Russia.
² Scientific and Educational Center 'Biomedical Technologies', School of Medical Biology, South Ural State University, Chelyabinsk 454080, Russia.
³ Federal Neurosurgical Center, Novosibirsk 630048, Russia.
⁴ Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
⁵ Institute of General Pathology and Pathophysiology, Moscow 125315, Russia.
⁶ Faculty of Basic Medicine, Chelyabinsk State University, Chelyabinsk 454080, Russia.
⁷ Laboratory of Neuroendocrinology, Pavlov Institute of Physiology, Saint Petersburg 199034, Russia.
⁸ Department of Physiology, Pavlov Institute of Experimental Medicine, Saint Petersburg 197376, Russia.
⁹ Zelman Institute of Medicine and Psychology, Novosibirsk State University, Novosibirsk 630090, Russia.

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.

Keywords: anxiety; cytokines; hepatocytes; inflammation; liver; mitochondria; oxidative stress; phenotypes; post-traumatic stress disorder; rats.

MeSH terms

Animals
Anxiety / etiology
Anxiety Disorders
Liver
Mitochondria
Rats
Stress Disorders, Post-Traumatic*

Grants and funding

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.