Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry-Based Metabolomics Reveals Metabolic Alterations in the Mouse Cerebellum During Toxoplasma gondii Infection

Ma, Jun; He, Jun-Jun; Hou, Junling; Zhou, Chun-Xue; Elsheikha, Hany M.; Zhu, Xingquan

doi:10.3389/fmicb.2020.01555

Cited by 8 publications

(6 citation statements)

References 51 publications

(59 reference statements)

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“…Saturated lipids contained in APOE and APOJ lipoparticles mediate A1 astrocyte-induced toxicity to oligodendrocytes 35 . Studies used T. gondii PRU strain demonstrated that from 7 days post-infection to 21 days post-infection, metabolites in the unsaturated fatty acid biosynthesis pathway in mouse cerebral cortex were upregulated as the infection progressed, indicating that T. gondii induces the biosynthesis of unsaturated fatty acids to promote its own growth and survival 36 , 37 . Thus, it is worthy of further study the linkage between TCI, host lipid metabolism and neuron damage/disfunction.…”

Section: Resultsmentioning

confidence: 99%

Observing astrocyte polarization in brains from mouse chronically infected with Toxoplasma gondii

Yao,

Yuan,

Sheng

et al. 2024

Sci Rep

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Toxoplasma gondii (T. gondii) is a protozoan parasite that infects approximately one-third of the global human population, often leading to chronic infection. While acute T. gondii infection can cause neural damage in the central nervous system and result in toxoplasmic encephalitis, the consequences of T. gondii chronic infection (TCI) are generally asymptomatic. However, emerging evidence suggests that TCI may be linked to behavioral changes or mental disorders in hosts. Astrocyte polarization, particularly the A1 subtype associated with neuronal apoptosis, has been identified in various neurodegenerative diseases. Nevertheless, the role of astrocyte polarization in TCI still needs to be better understood. This study aimed to establish a mouse model of chronic TCI and examine the transcription and expression levels of glial fibrillary acidic protein (GFAP), C3, C1q, IL-1α, and TNF-α in the brain tissues of the mice. Quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay, and Western blotting were employed to assess these levels. Additionally, the expression level of the A1 astrocyte-specific marker C3 was evaluated using indirect fluorescent assay (IFA). In mice with TCI, the transcriptional and expression levels of the inflammatory factors C1q, IL-1α, and TNF-α followed an up-down-up pattern, although they remained elevated compared to the control group. These findings suggest a potential association between astrocyte polarization towards the A1 subtype and synchronized changes in these three inflammatory mediators. Furthermore, immunofluorescence assay (IFA) revealed a significant increase in the A1 astrocytes (GFAP+C3+) proportion in TCI mice. This study provides evidence that TCI can induce astrocyte polarization, a biological process that may be influenced by changes in the levels of three inflammatory factors: C1q, IL-1α, and TNF-α. Additionally, the release of neurotoxic substances by A1 astrocytes may be associated with the development of TCI.

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Section: Resultsmentioning

confidence: 99%

Observing astrocyte polarization in brains from mouse chronically infected with Toxoplasma gondii

Yao,

Yuan,

Sheng

et al. 2024

Sci Rep

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“…Previous studies revealed how the metabolism of T. gondii and the host is altered after infection (Blume et al 2009 , 2015 ; Ma et al 2019 , 2020 , 2021 ; Olson et al 2020 ). In the present study, we have shown that T. gondii infection changes the host cells’ metabolism by altering the expression of circRNAs involved in TCA cycle, metabolic pathways, fatty acid metabolism, glutathione metabolism, and glycolysis/gluconeogenesis.…”

Section: Discussionmentioning

confidence: 99%

Expression profiles of host miRNAs and circRNAs and ceRNA network during Toxoplasma gondii lytic cycle

Wang,

et al. 2024

Parasitol Res

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Toxoplasma gondii is an opportunistic protozoan parasite that is highly prevalent in the human population and can lead to adverse health consequences in immunocompromised patients and pregnant women. Noncoding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), play important regulatory roles in the pathogenesis of many infections. However, the differentially expressed (DE) miRNAs and circRNAs implicated in the host cell response during the lytic cycle of T. gondii are unknown. In this study, we profiled the expression of miRNAs and circRNAs in human foreskin fibroblasts (HFFs) at different time points after T. gondii infection using RNA sequencing (RNA-seq). We identified a total of 7, 7, 27, 45, 70, 148, 203, and 217 DEmiRNAs and 276, 355, 782, 1863, 1738, 6336, 1229, and 1680 DEcircRNAs at 1.5, 3, 6, 9, 12, 24, 36, and 48 h post infection (hpi), respectively. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that the DE transcripts were enriched in immune response, apoptosis, signal transduction, and metabolism-related pathways. These findings provide new insight into the involvement of miRNAs and circRNAs in the host response to T. gondii infection.

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“…Alterations in the lipid and protein contents of hBMECs have been previously detected using proton nuclear magnetic resonance-based metabolomic analysis [ 7 , 9 ]. In addition, changes in the abundance of lipids (e.g., glycerophospholipid) and amino acid (phenylalanine, retinol, and tryptophan) were detected in mouse cerebellum during T. gondii infection by using ultra performance liquid chromatography-tandem mass spectrometry-based metabolomics [ 28 ]. However, the application of these methods requires a special sample preparation, which may alter the biochemical composition of the host cells.…”

Section: Discussionmentioning

confidence: 99%

Illuminating Host-Parasite Interaction at the Cellular and Subcellular Levels with Infrared Microspectroscopy

Elsheikha

Al-sandaqchi

Harun

et al. 2022

Cells

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Toxoplasma gondii (T. gondii) is an opportunistic protozoan that can cause brain infection and other serious health consequences in immuno-compromised individuals. This parasite has a remarkable ability to cross biological barriers and exploit the host cell microenvironment to support its own survival and growth. Recent advances in label-free spectroscopic imaging techniques have made it possible to study biological systems at a high spatial resolution. In this study, we used conventional Fourier-transform infrared (FTIR) microspectroscopy and synchrotron-based FTIR microspectroscopy to analyze the chemical changes that are associated with infection of human brain microvascular endothelial cells (hBMECs) by T. gondii (RH) tachyzoites. Both FTIR microspectroscopic methods showed utility in revealing the chemical alterations in the infected hBMECs. Using a ZnS hemisphere device, to increase the numerical aperture, and the synchrotron source to increase the brightness, we obtained spatially resolved spectra from within a single cell. The spectra extracted from the nucleus and cytosol containing the tachyzoites were clearly distinguished. RNA sequencing analysis of T. gondii-infected and uninfected hBMECs revealed significant changes in the expression of host cell genes and pathways in response to T. gondii infection. These FTIR spectroscopic and transcriptomic findings provide significant insight into the molecular changes that occur in hBMECs during T. gondii infection.

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Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry-Based Metabolomics Reveals Metabolic Alterations in the Mouse Cerebellum During Toxoplasma gondii Infection

Cited by 8 publications

References 51 publications

Observing astrocyte polarization in brains from mouse chronically infected with Toxoplasma gondii

Observing astrocyte polarization in brains from mouse chronically infected with Toxoplasma gondii

Expression profiles of host miRNAs and circRNAs and ceRNA network during Toxoplasma gondii lytic cycle

Illuminating Host-Parasite Interaction at the Cellular and Subcellular Levels with Infrared Microspectroscopy

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