Thesis
T. gondii chronic and congenital infection and host manipulation : behavioural, immunological and metabolomics consequences in the brain
- Creator
- Awarding institution
- University of Strathclyde
- Date of award
- 2012
- Thesis identifier
- T13464
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Previous studies have demonstrated that Toxoplasma gondii infection changes behaviour in rodents. In humans, T. gondii is considered a possible environmental and neurodevelopment risk factor for the pathogenesis of psychiatric disorders. During chronic infection T. gondii can form cysts in the brain, an optimal site to mediate these effects. Herein, the ability of T. gondii infection to alter murine behaviour was assessed in both adult acquired chronically infected, congenitally infected mice and in mice exposed to the maternal immune response to T. gondii infection during gestation. The immune-neuro environment of these mice was investigated by measuring the levels of cytokine and tryptophan metabolism transcripts by quantitative RT-PCR and the levels of identified metabolites by mass spectrometry. Hyperactivity and lower anxiety levels were observed in chronically infected mice. Higher anxiety levels were observed in congenitally infected mice and hyperactivity was measured in the mice exposed to maternal immune activation during T. gondii infection. Changes were also observed in the neuro-immune environment; in particular upregulation of inflammatory cytokines and higher levels of KYNA metabolites, which are known to be neurotoxic, were detected in the chronically adult acquired and congenitally infected mice. Instead, a down regulation of the immune mediators was measured in the brain samples of mice exposed to maternal immune activation. Hyperactivity of amino acid metabolism was observed in the metabolomic profiling of the brain samples from all groups of mice infected with T. gondii . Although it cannot at present be determined if the changes in the brain chemistry caused by congenitally acquired T. gondii infection are induced via the immune response or are directly mediated by the parasite. However, the studies described here provide a better understanding of how the parasite can influence behaviours and provide possible insights into new therapeutically approaches for treatment of mental health and degenerative disorders.
- Resource Type
- Note
- Strathclyde theses - ask staff. Thesis no. : T13464
- DOI
- Date Created
- 2012
- Former identifier
- 991158
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