The relationship between the infection of Toxoplasma gondii and Alzheimer’s disease

dc.contributor.advisorProf. Geoff Hide
dc.contributor.authorBADER SALEEM M ALAWFI
dc.date2021 microbiology of Salford
dc.description.abstractToxoplasma gondii is a zoonotic parasite that commonly causes infections in a variety of warm-blooded animals including humans. This parasite causes a disease referred to as toxoplasmosis. T. gondii infections are known to have a significant impact on the host brain since the parasite can penetrate the blood-brain barrier and extensively colonize the central nervous system (CNS) for an extended period. Attacks of the brain tissue by the parasite can cause both neurological and structural damage. The parasite infects the brain, forms a cyst and affects several parts of the brain, including the amygdala, hippocampus, other cortical regions, and cerebellum; this can result in alterations in the hosts' behaviour. Studies have proposed that infections caused by T. gondii pose a risk in the development of several neuropsychiatric disorders like Alzheimer’s disease, Schizophrenia, and Parkinson's disease. The aims of this study were to conduct a pilot study on the association between T. gondii infections and Alzheimer's disease using tissue samples from the Manchester Brain Bank (MBB) and to investigate the effect of the parasite on oxidative stress in cultured human brain cells As a pilot study, previously prepared slides from 124 brain sections from Alzheimer’s patients and controls were examined for the presence of Toxoplasma gondii cysts. Despite a 10% prevalence of T. gondii in humans in the UK, no cysts were detected in any of the sections. It was concluded that unsustainably large tissue samples would be required from MBB to pursue an investigation using this approach. Instead, a line of investigation was pursued that explored the interactions between T. gondii infections and oxidative stress (a feature of neurological diseases such as Alzheimer's) using the development of a model system. SH-SY5Y cells were used as culture models for neuronal cells and flow cytometry and MTT assays were conducted to determine cell viability. To evaluate the effects of oxidative stress, differentiated and undifferentiated SH-SY5Y cells, were examined for cell viability and the effects of infection by T. gondii type I and II were investigated. When high doses of H2O2 [250 and 500𝜇M) were used for 24 hours in undifferentiated SH-SY5Y cells, there was a reduction in the cell viability to 8.66% and 4.66% respectively. Conversely, when SH-SY5Y cells (differentiated) were subjected to high doses of H2O2 (250 and 500𝜇M) a much reduced decline in cell viability, to 64.6% and 39.33% respectively, occurred. The effects of T. gondii strain I and II infections on oxidative stress in both undifferentiated and differentiated cells were also investigated. The outcome showed that pre-treatment of the undifferentiated and differentiated cells with T. gondii weakened the H2O2 effect on the viability of SH-SY5Y cells such that cell viability (85.75%) was significantly higher than in cells treated with only H2O2 (25.25%) or cells post-treated (28%) by infection with T. gondii. Further results demonstrated that pre-treatment of the undifferentiated SH-SY5Y cells using T. gondii strain I and II CM (conditioned media) led to a significant decrease in the H2O2 -induced cell damage and apoptosis. In conclusion, this study demonstrates that differentiated SH-SY5Y cells show higher resistance towards oxidative stress that induces cell damage and death as compared to undifferentiated SH-SY5Y cells. Interestingly, infection with T. gondii results in anti-oxidative effects on neuronal cells which may protect against cell damage. These results suggest that infection with this parasite could protect against neurological diseases such as Alzheimer's disease.
dc.titleThe relationship between the infection of Toxoplasma gondii and Alzheimer’s disease
sdl.thesis.sourceSACM - United Kingdom