Toxoplasma gondii induces metabolic disturbances in the hippocampus of BALB/c mice

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.