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The pathogenic potential of the combined action of chronic Opisthorchis felineus infection and repeated social defeat stress in C57BL/6 mice
International Journal for Parasitology ( IF 3.7 ) Pub Date : 2020-12-27 , DOI: 10.1016/j.ijpara.2020.10.003
Damira Avgustinovich 1 , Anna Kovner 2 , Elena Kashina 3 , Natalia Shatskaya 2 , Galina Vishnivetskaya 2 , Natalia Bondar 4 , Maria Lvova 2
Affiliation  

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.



中文翻译:

C57BL/6小鼠慢性猫后睾感染和反复社交失败应激共同作用的致病潜力

寄生性食源性疾病和慢性社会压力是人类日常生活的常见特征。因此,我们的目的是模拟慢性猫后睾丸的联合作用C57BL/6 小鼠的感染和反复社交失败压力。肝脏的组织学检查显示受感染小鼠的炎症部位、明显的导管周围纤维化和胆管纤维化以及胆管增殖和肝细胞营养不良,特别是在暴露于压力的小鼠中。在肝脏病理学的同时,我们检测到大脑皮层的显着结构变化。海马的免疫组织化学分析表明,在同时受到两种不利因素影响的小鼠中,Iba 1-、IL-6-、iNOS-和 Arg1 阳性细胞的数量密度增加最高。在反复社交失败压力期间,GFAP 阳性细胞的数量增加,在受到感染和压力的小鼠中最为明显。实时荧光定量 PCR 分析表明基因Aif1的表达Il6在分析的大脑区域(海马、下丘脑和额叶皮层)之间存在差异,并且取决于所应用的不利因素。此外,在脑区中,当两种不良治疗联合时,这些参数没有一致的增加或减少:(i)在海马中,Aif1上调,而Il6表达没有变化;(ii) 在下丘脑中,Aif1Il6 的表达水平与对照没有区别;(iii) 在额叶皮层,Aif1表达没有变化,而Il6表达增加。可以得出结论,两个长期存在的不利因素的结合,O. felineus感染和反复的社交失败压力不仅会恶化肝脏状态,还会恶化大脑状态,正如小鼠惊吓反应的紊乱所证明的那样。

更新日期:2020-12-27
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