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Title: Immune response effect on dopamine production during Toxoplasma gondii infection
Author: Alsaady, Isra Mohhammed
ISNI:       0000 0004 6351 6768
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2016
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Many recent studies have developed our understanding of Toxoplasma gondii and host interactions whilst in the brain as well as the mechanisms that the parasite uses to change the behaviour of the host, since the parasite was found to increase dopamine production in catecholaminergic cells (PC12). Indeed, in vivo staining of the parasite cyst found dopamine accumulation inside the cysts. However, a detailed mechanism of dopamine production and the immune response involvement to dopamine levels is not yet clear. Several approaches have been used is this study to gain a better understanding. Firstly, immunostaining and mRNA expression have revealed that culturing T. gondii in tryptophan free media induces tachyzoite to bradyzoite differentiation. Secondly, analysis of the effect of kynurenic acid (KYNA) on dopamine levels showed that the parasite blocks the suppression of dopamine levels by KYNA through interfering with KYNA-induced changes in phosphorylation of tyrosine hydroxylase. Finally, host-parasite dynamics were examined by RNA sequencing (RNA-Seq) of T. gondii infected neurotransmitter-expressing cell. Our data found that the parasite does not increase dopamine production alone, but also modifies catecholamine metabolism to increase dopamine production and decrease norepinephrine and epinephrine; these modifications together with changes in expression of genes encoding dopamine receptors, neuronal function, neurodevelopmental, and NMDR suggest mechanisms of host neurotransmission modification. RNA-Seq data also revealed changes in the immune response of infected neural cells with subversion in expression of host cell cytokines and chemotaxis i. RNA-Seq data also show the simultaneous change in T. gondii expression during neural cell infection and showed that this profile is distinct from the expression profile in other host cells.
Supervisor: McConkey, Glenn Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available