Thesis
A systems approach to determine how Toxoplasma gondii Infection causes neuropsychiatric disease
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2019
- Thesis identifier
- T15515
- Person Identifier (Local)
- 201671340
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- T. gondii infection acquired during life has been associated with psychoneurological disease in humans and behavioural changes in mice. However, less is known about the potential of congenitally acquired T. gondii infection, or for maternal T. gondii infection induced immune activation, to cause psychoneurological disease. The studies described herein, using LCMS (Liquid chromatography–mass spectrometry) demonstrate that adult acquired infection alters the neurochemistry and transcriptome of the brains of BALB/c mice. Notable changes to tryptophan, purine, arginine and carnitine metabolism were observed in infected mice. Congenitally infected and mice exposed to the maternal immune response to T. gondii, but not congenitally infected were found to have decreased mobility compared with control mice. Congenital T. gondii infection resulted in similar alterations in the neurochemistry of mice as seen in adult acquired infections. Some of these changes were observed, including tryptophan metabolism in mice exposed to the maternal immune response to T. gondii, but not congenitally infected. Both adult acquired T. gondii and congenital infection altered the brain transcriptome of mice relative to control uninfected mice with notable changes seen to transcripts of many immunologically important genes and enzymes in some of the metabolic pathways identified by LCMS. In addition, both adult acquired T. gondii infection, congenital infection and maternal exposure to different degrees were found to induce changes in a number of additional transcripts previously associated with psychoneurological diseases. These results demonstrate that maternal exposure to T. gondii infection during pregnancy induces a subset of neurochemical and transcriptomic changes found in mice with adult acquired and congenital T. gondii infection. The results therefore reinforce the potential of maternal immune activation to affect psychoneurological diseases and implicate T. gondii as a potential aetiological agent of this process.
- Advisor / supervisor
- Roberts, Craig
- Resource Type
- Note
- This thesis was previously held under moratorium from 16/03/2020 to 16/03/2022
- DOI
- Date Created
- 2019
- Former identifier
- 9912787793002996
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