Abstract
Toxoplasma gondii can cross the blood-brain barrier and infect different regions of the brain including the hippocampus. In the present study, we examined the impact of Toxoplasma gondii infection on the metabolism of the hippocampus of female BALB/c mice compared to control mice using ultra-high-performance liquid chromatography-tandem mass spectrometry. Multivariate analysis revealed significant differences between infected and control hippocampi and identified 25, 82, and 105 differential metabolites (DMs) in the infected hippocampi at 7, 14, and 21 days post-infection (dpi), respectively. One DM (sphingosyl-phosphocholine in the sphingolipid metabolism pathway) and 11 dysregulated pathways were detected at all time points post-infection, suggesting their important roles in the neuropathogenesis of T. gondii infection. These pathways were related to neural activity, such as inflammatory mediator regulation of TRP channels, retrograde endocannabinoid signaling, and arachidonic acid metabolism. Weighted correlation network analysis and receiver operating characteristic analysis identified 33 metabolites significantly associated with T. gondii infection in the hippocampus, and 30 of these were deemed as potential biomarkers for T. gondii infection. This study provides, for the first time, a global view of the metabolic perturbations that occur in the mouse hippocampus during T. gondii infection. The potential relevance of the identified metabolites and pathways to the pathogenesis of cognitive impairment and psychiatric disorders are discussed.
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Data availability
The metabolomics raw data have been deposited in the MetaboLights database (Access number: MTBLS1890).
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Acknowledgements
The authors would like to acknowledge the technical assistance, including metabolite extraction, identification, and quantification, provided by BGI-Shenzhen, China.
Funding
This work was supported, in part, by the National Natural Science Foundation of China (Grant No. 31902291), the National Key Research and Development Program of China (Grant No. 2017YFD0500403), the Yunnan Expert Workstation (Grant No. 202005AF150041), and the Veterinary Public Health Innovation Team of Yunnan Province.
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All mice were handled strictly in accordance with the Animal Ethics Procedures and Guidelines of the People’s Republic of China. The study’s protocol was reviewed and approved by the Animal Ethics Committee of Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (Permit No. LVRIAEC2017-06).
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Table S1
Details of the identified differentially abundant metabolites. (XLSX 50 kb)
Fig. S1
Agarose gel electrophoresis showing the presence of PCR products of Toxoplasma gondii B1 gene in the hippocampi of infected mice at 7, 14 and 21 days post infection (dpi). As anticipated, no amplicons were detected in the hippocampus of uninfected (control) mice. N: PCR negative control; P: T. gondii PCR positive control; M: DL1000 DNA marker (TAKARA, Dalian, China). (PNG 39 kb)
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Ma, J., He, JJ., Wang, M. et al. Toxoplasma gondii induces metabolic disturbances in the hippocampus of BALB/c mice. Parasitol Res 120, 2805–2818 (2021). https://doi.org/10.1007/s00436-021-07222-8
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DOI: https://doi.org/10.1007/s00436-021-07222-8