Interactions of Toxoplasma gondii with the central nervous system and neurological dysfunction

Pathogens, including viruses and parasites, manipulate the host’s system to enhance their ability to cause infection. One such parasite is Toxoplasma gondii, a protozoan parasite that has felines as the only definitive host. Studies of infected mice, the parasite’s intermediate host, have shown behavioural changes in the host during infection, resulting in easy predation of the intermediate host by the definitive host. It has been shown that T. gondii modulates dopamine and glutamine in the infected host, while the location and distribution of T. gondii cysts in the brain may mediate changes in behaviour. T. gondii has been associated with schizophrenia and bipolar disorder and may play a role in other neural disorders, such as Parkinson’s disease (PD) that affects dopaminergic neurones. During this dissertation, a possible correlation between T. gondii and PD was investigated with anti-Toxoplasma gondii IgG detection in PD (n=206) and control (n=176) samples. Anti-T. gondii IgG was detected in both PD and controls with almost identical seropositivity. Secondly, to understand the involvement of T. gondii in neurological disorders, behavioural studies and neurotransmitter analysis performed on T. gondii-infected mice that had been bred for a heterozygous mutation in the neurexin-1 gene, which has been linked to schizophrenia. T. gondii infected mice showed less anxiolytic behaviours and sociability, but no obvious combined effect of T. gondii and neurexin-1 mutation was detected. Finally, rat brain cysts were located and quantitated in the brains of 109 infected rats. T. gondii cysts showed some tropism toward the cerebellum, cerebral cortex, colliculus and thalamus, although encysted parasites were found in all brain regions. This study increases our understanding of the potential mechanisms this parasite has developed to achieve specific manipulation of the intermediate host to increase transmission success to the feline definitive host; this has implications for the impact of infection on the health and behaviour of infected mammals, including humans.