TY - JOUR

T1 - The pathogenic potential of the combined action of chronic Opisthorchis felineus infection and repeated social defeat stress in C57BL/6 mice

AU - Avgustinovich, Damira

AU - Kovner, Anna

AU - Kashina, Elena

AU - Shatskaya, Natalia

AU - Vishnivetskaya, Galina

AU - Bondar, Natalia

AU - Lvova, Maria

N1 - Funding Information: This work was supported by the Russian Foundation for Basic Research (grant No. 20-04-00139), by the state program of the Federal Research Center ICG SB RAS , Russia (No. 0324-2019-0041-C-01 ), and a project within a state assignment (No. 0301-2019-0005 ) for the Institute of Solid State Chemistry and Mechanochemistry , SB RAS. The authors are grateful to the Multi-access Center for Microscopy of Biological Objects, Russia ( http://www.bionet.nsc.ru/microscopy/ ) and to the Center for Genetic Resources of Laboratory Animals of the Federal Research Center ICG SB RAS (supported by the Ministry of Science and Higher Education of Russia; unique identifier of the project: RFMEFI62119X0023) for access to equipment and animals. We are thankful to Nikolai Shevchuk ( http://shevchuk-editing.com ) for English language editing of this manuscript (Language Certificate dated 2 June, 2020). The authors also thank Alena Kizimenko and Maria Marenina for assistance with the preparation of Supplementary Fig. S1 A and B. Publisher Copyright: © 2020 Australian Society for Parasitology Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/4

Y1 - 2021/4

N2 - Parasitic food-borne diseases and chronic social stress are frequent attributes of day-to-day human life. Therefore, our aim was to model the combined action of chronic Opisthorchis felineus infection and repeated social defeat stress in C57BL/6 mice. Histological examination of the liver revealed inflammation sites, pronounced periductal fibrosis, and cholangiofibrosis together with proliferation of bile ducts and hepatocyte dystrophy in the infected mice, especially in the stress-exposed ones. Simultaneously with liver pathology, we detected significant structural changes in the cerebral cortex. Immunohistochemical analysis of the hippocampus indicated the highest increase in numerical density of Iba 1-, IL-6-, iNOS-, and Arg1-positive cells in mice simultaneously subjected to the two adverse factors. The number of GFAP-positive cells rose during repeated social defeat stress, most strongly in the mice subjected to both infection and stress. Real-time PCR analysis showed that the expression of genes Aif1 and Il6 differed among the analysed brain regions (hippocampus, hypothalamus, and frontal cortex) and depended on the adverse factors applied. In addition, among the brain regions, there was no consistent increase or decrease in these parameters when the two adverse treatments were combined: (i) in the hippocampus, there was upregulation of Aif1 and no change in Il6 expression; (ii) in the hypothalamus, expression levels of Aif1 and Il6 were not different from controls; and (iii) in the frontal cortex, Aif1 expression did not change while Il6 expression increased. It can be concluded that a combination of two long-lasting adverse factors, O. felineus infection and repeated social defeat stress, worsens not only the hepatic but also brain state, as evidenced behaviorally by disturbances of the startle response in mice.

AB - Parasitic food-borne diseases and chronic social stress are frequent attributes of day-to-day human life. Therefore, our aim was to model the combined action of chronic Opisthorchis felineus infection and repeated social defeat stress in C57BL/6 mice. Histological examination of the liver revealed inflammation sites, pronounced periductal fibrosis, and cholangiofibrosis together with proliferation of bile ducts and hepatocyte dystrophy in the infected mice, especially in the stress-exposed ones. Simultaneously with liver pathology, we detected significant structural changes in the cerebral cortex. Immunohistochemical analysis of the hippocampus indicated the highest increase in numerical density of Iba 1-, IL-6-, iNOS-, and Arg1-positive cells in mice simultaneously subjected to the two adverse factors. The number of GFAP-positive cells rose during repeated social defeat stress, most strongly in the mice subjected to both infection and stress. Real-time PCR analysis showed that the expression of genes Aif1 and Il6 differed among the analysed brain regions (hippocampus, hypothalamus, and frontal cortex) and depended on the adverse factors applied. In addition, among the brain regions, there was no consistent increase or decrease in these parameters when the two adverse treatments were combined: (i) in the hippocampus, there was upregulation of Aif1 and no change in Il6 expression; (ii) in the hypothalamus, expression levels of Aif1 and Il6 were not different from controls; and (iii) in the frontal cortex, Aif1 expression did not change while Il6 expression increased. It can be concluded that a combination of two long-lasting adverse factors, O. felineus infection and repeated social defeat stress, worsens not only the hepatic but also brain state, as evidenced behaviorally by disturbances of the startle response in mice.

KW - C57BL/6 mice

KW - IL-6

KW - Liver

KW - Microglia

KW - Opisthorchis felineus

KW - Social stress

KW - Startle response

UR - http://www.scopus.com/inward/record.url?scp=85099149379&partnerID=8YFLogxK

U2 - 10.1016/j.ijpara.2020.10.003

DO - 10.1016/j.ijpara.2020.10.003

M3 - Article

C2 - 33378706

AN - SCOPUS:85099149379

VL - 51

SP - 353

EP - 363

JO - International Journal for Parasitology

JF - International Journal for Parasitology

SN - 0020-7519

IS - 5

ER -