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大脑对伯氏疟原虫感染反应中的性别差异影响

Impact of sex differences in brain response to infection with Plasmodium berghei.

作者信息

Dkhil Mohamed A, Al-Shaebi Esam M, Lubbad Mahmoud Y, Al-Quraishy Saleh

机构信息

Department of Zoology, College of Science, King Saud University, P.O. Box: 2455, Riyadh, 11451, Saudi Arabia.

Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt.

出版信息

Parasitol Res. 2016 Jan;115(1):415-22. doi: 10.1007/s00436-015-4803-6. Epub 2015 Oct 24.

DOI:10.1007/s00436-015-4803-6
PMID:26499384
Abstract

Malaria is considered to be one of the most prevalent diseases in the world. Severity of the disease between males and females is very important in clinical research areas. In this study, we investigated the impact of sex differences in brain response to infection with Plasmodium berghei. Male and female C57Bl/6 mice were infected with P. berghei-infected erythrocytes. The infection induced a significant change in weight loss in males (-7.2 % ± 0.5) than females (-4.9 % ± 0.6). The maximum parasitemia reached about 15 % at day 9 postinfection. Also, P. berghei infection caused histopathological changes in the brain of mice. These changes were in the form of inflammation, hemorrhage, and structural changes in Purkinje cells. In addition, P. berghei was able to induce a marked oxidative damage in mice brain. The infection induced a significant increase in male brain glutathione than females while the brain catalase level was significantly increased in infected females than infected males. Moreover, the change in brain neurotransmitters, dopamine, epinephrine, norepinephrine, and serotonin, was more in infected males than infected females. At the molecular level, P. berghei was able to induce upregulations of Adam23, Cabp1, Cacnb4, Glrb, and Vdac3-mRNA in the brain of mice. These genes were significantly upregulated in infected males than in infected females. In general, P. berghei could induce structural, biochemical, and molecular alterations in mice brain. Severity of these alterations was different according to sex of mice.

摘要

疟疾被认为是世界上最普遍的疾病之一。在临床研究领域,该疾病在男性和女性之间的严重程度非常重要。在本研究中,我们调查了性别差异对感染伯氏疟原虫后脑反应的影响。将雄性和雌性C57Bl/6小鼠感染感染了伯氏疟原虫的红细胞。感染导致雄性小鼠体重减轻的变化(-7.2%±0.5)比雌性小鼠(-4.9%±0.6)更为显著。感染后第9天,最大寄生虫血症达到约15%。此外,伯氏疟原虫感染导致小鼠大脑出现组织病理学变化。这些变化表现为炎症、出血以及浦肯野细胞的结构变化。此外,伯氏疟原虫能够在小鼠大脑中诱导明显的氧化损伤。感染导致雄性大脑中的谷胱甘肽显著增加,而感染雌性小鼠大脑中的过氧化氢酶水平比感染雄性小鼠显著升高。此外,感染雄性小鼠大脑中神经递质多巴胺、肾上腺素、去甲肾上腺素和血清素的变化比感染雌性小鼠更为明显。在分子水平上,伯氏疟原虫能够诱导小鼠大脑中Adam23、Cabp1、Cacnb4、Glrb和Vdac3-mRNA的上调。这些基因在感染雄性小鼠中比在感染雌性小鼠中显著上调。总体而言,伯氏疟原虫可诱导小鼠大脑发生结构、生化和分子改变。这些改变的严重程度因小鼠性别而异。

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