Thesis
A metabolomics approach to determine how Toxoplasma gondii infection causes neuropsychiatric disease
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2015
- Thesis identifier
- T14152
- Person Identifier (Local)
- 201366955
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- The following studies were undertaken with the aim of investigating changes in brain metabolism that might account for Toxoplasma gondii induced behavioural modifications in BALB/c mice. Liquid Chromatography-Mass Spectroscopy (LCMS) analyses of brains from infected and control mice detected 783 putative metabolites. A number of metabolic pathways were found to be altered in the brains of infected mice relative to control uninfected mice including the Citrate cycle, Glycolysis, Arginine metabolism, Tryptophan metabolism and Purine metabolism. The upregulation of metabolites in glycolysis and the citrate cycle is indicative of the extra energy requirements of an immune response. As nitric oxide (NO) has been demonstrated to play a protective role during T. gondii infection arginine metabolism was explored in this study. No consistent significant differences in arginine, argininosuccinate, citrulline, ornithine or proline were detected. A number of metabolites resulting from Tryptophan degradation including formyl-kynurenine, kynurenine, indolelactate, and quinolinic acid were consistently raised in the brains of infected mice relative to control mice. Formyl-kynurenine, kynurenine and indolelactate were significantly raised throughout both experimental runs at 4 weeks post-infection (p<0.01, p<0.01, p<0.01, respectively in run 1; p<0.01, p<0.01, p<0.05, respectively in run 2). Formyl-kynurenine and kynurenine remained significantly raised at 8 weeks post-infection (p<0.01 and p<0.05 respectively in run 1; p<0.05 and p<0.01 respectively in run 2). Purine degradation was evident in the brains of infected mice which had significantly reduced adenine and adenosine levels but increased levels of xanthosine and urate. In conclusion, these observations support a potential role for T. gondii-induced degradation of tryptophan and purine in mediating behavioural changes in mice. The results therefore give insight into global changes in host neurometabolism during T. gondii infection and suggest potential mechanisms that might account for T. gondii induced behavioural changes in mice including changes to tryptophan and purine metabolism. Some of the mechanisms could have relevance for the apparent association of T. gondii infection with neuropsychiatric disease in humans, including schizophrenia.
- Resource Type
- DOI
- Date Created
- 2015
- Former identifier
- 1238475
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File | 2021-07-02 | University of Strathclyde |