A systems approach to determine how Toxoplasma gondii Infection causes neuropsychiatric disease

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.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral-pg

Grantor dc:publisher.institution

University of Strathclyde

Year dc:date.issued

2019

Author dc:creator

• Abdelsalam, Aisha A Abdelati

Advisor dc:contributor.advisor

• Roberts, Craig

DOI

10.48730/xqaw-5v54

Identifier

T15515

Author Identifier

201671340

OAI identifier oai:identifier

oai:strathclyde:th83kz33c