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白藜芦醇对感染克氏锥虫的小鼠胚胎神经祖细胞分化命运的影响。

Effects of resveratrol on the differentiation fate of neural progenitor cells of mouse embryos infected with Trypanosoma cruzi.

机构信息

Graduate Program in Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil.

Graduate Program in Veterinary Medicine, Department of Parasitology, Microbiology and Immunology, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil; Instituto Federal Farroupilha (IFFar), Campus Frederico Westphalen, RS, Brazil.

出版信息

Microb Pathog. 2019 Jul;132:156-161. doi: 10.1016/j.micpath.2019.04.040. Epub 2019 Apr 25.

Abstract

Chagas disease (CD) affecting about 7 million people is caused by the flagellate protozoan Trypanosoma cruzi. The central nervous system (CNS) is an important site for T. cruzi persistence in the host during the chronic phase of infection, because the protozoan may pass the blood-brain barrier and may cause motor and cognitive neuronal damage. Thinking about avoiding or minimizing these negative effects, it is hypothesized that resveratrol (RSV), a component with several medicinal properties has beneficial effects on the CNS. The objective of this study was to investigate, whether T. cruzi infection interferes with neurogenesis and gliogenesis of embryos of infected mice females, and whether RSV would be able to avoid or minimize these changes caused by CD. RSV is a polyphenol found in grapes and widely studied for its neuroprotective and antioxidant properties. In addition, we investigated the role caused by the parasite during congenital infection and CNS development. Embryos and their brains were PCR-positive for T. cruzi. For this study, NPCs obtained from telencephalon of infected and uninfected embryos and were cultured in presence of resveratrol for forming neurospheres. The results demonstrated that the congenital transmission of T. cruzi influences CNS formation and neural fate, decreasing the number of neuroespheres and causing an elongation in the phases of the cell cycle. In addition, the parasite promoted an increase in neugliogenesis. Resveratrol was neuroprotective and prevented negative effects of the infection. Thus, we suggest the use of resveratrol as a therapeutic target for the treatment of neuroinflammation or as neuroprotective agent during Chagas disease, as it improves gliogenesis and restores neural migration.

摘要

克氏锥虫引起的恰加斯病(CD)影响约 700 万人,是一种鞭毛原生动物。在感染的慢性期,中枢神经系统(CNS)是寄生虫在宿主体内持续存在的重要部位,因为原生动物可能穿过血脑屏障,并可能导致运动和认知神经元损伤。考虑到避免或最小化这些负面影响,有人假设白藜芦醇(RSV)作为一种具有多种药用特性的成分对 CNS 有有益作用。本研究旨在探讨克氏锥虫感染是否会干扰感染雌鼠胚胎的神经发生和神经胶质发生,以及 RSV 是否能够避免或最小化 CD 引起的这些变化。RSV 是一种存在于葡萄中的多酚,因其具有神经保护和抗氧化特性而被广泛研究。此外,我们还研究了寄生虫在先天性感染和中枢神经系统发育过程中所起的作用。胚胎及其大脑对 T. cruzi 呈 PCR 阳性。为此,我们从感染和未感染胚胎的端脑中获得 NPCs,并在 RSV 存在的情况下培养以形成神经球。结果表明,克氏锥虫的先天性传播会影响中枢神经系统的形成和神经命运,减少神经球的数量,并导致细胞周期的各个阶段延长。此外,寄生虫还促进了神经胶质的新生。RSV 具有神经保护作用,可防止感染的负面影响。因此,我们建议将 RSV 用作治疗神经炎症的治疗靶点或作为恰加斯病期间的神经保护剂,因为它可以改善神经胶质发生并恢复神经迁移。

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