The role of parasite-produced dopamine in Toxoplasma gondii-altered host behaviour
Authors: Beatriz Calvo-Urbano (University of London, Royal Veterinary College), Maya Kaushik (Imperial College London), An-Chi Cheng (University of London, Royal Veterinary College), Greg C. Bristow (University of Leeds, University of Bradford), Emese Prandovszky (University of Leeds, Johns Hopkins University), Martin Walker (University of London, Royal Veterinary College), Poppy H. L. Lamberton (Imperial College London, University of Glasgow), Glenn A. McConkey (University of Leeds), Joanne P. Webster (University of London, Royal Veterinary College)
Abstract
Abstract Certain parasites appear to manipulate their host’s behaviour for their own selective benefit. The mechanisms behind such behavioural alterations in vertebrate hosts remain elusive, despite their profound implications, particularly for those parasites with a broad host range. Toxoplasma gondii , the causative agent of the globally important toxoplasmosis, is a canonical example for parasite-altered behaviour in its rodent intermediate host. Such behavioural alterations, from subtle to severe, are also displayed across a broad spectrum of infected secondary hosts, including humans. Dopamine dysregulation has been proposed as one potential mechanistic explanation. Furthermore, T. gondii was found to encode tyrosine hydroxylases, Tg TH, suggesting that the parasite itself may be a source of dopamine. The role of Tg TH in behaviour change, however, remains controversial, with currently no behavioural studies supporting a direct link. Here, using the biologically and clinically appropriate rat ( Rattus norvegicus ) model, with subtle and specific behavioural and biostatistical assays and analyses, we aimed to elucidate the role of Tg TH on host behavioural change. For this purpose, we developed two differentially (middle and high) over-expressing (OE) Prugniaud T. gondii lines, for comparison with both a true wildtype and a recombinant wildtype, without Tg TH modification, as well as uninfected negative (sham exposed) controls. Our results indicated that, whilst all genetically modified parasite lines induced smaller intensities of behavioural change relative to true wild-type T. gondii , potentially indicative of lowered fitness of the recombinant lines in general, the severity of behavioural changes were dose-dependent on the level of Tg TH expression. Our findings thereby provide unique support for the hypothesis of a contributing mechanistic role of Tg TH in T. gondii -associated behavioural changes, and we discuss these findings in terms of their theoretical and applied implications.
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Closest papers
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The Neurotropic Parasite Toxoplasma Gondii Increases Dopamine MetabolismE. Prandovszky, Elizabeth Gaskell, H. Martin et al. · 2011 · PLoS ONE · Not summarized yet
Abstract
The highly prevalent parasite Toxoplasma gondii manipulates its host's behavior. In infected rodents, the behavioral changes increase the likelihood that the parasite will be transmitted back to its definitive cat host, an essential step in completion of the parasite's life cycle. The mechanism(s) responsible for behavioral changes in the host is unknown but two lines of published evidence suggest that the parasite alters neurotransmitter signal transduction: the disruption of the parasite-induced behavioral changes with medications used to treat psychiatric disease (specifically dopamine antagonists) and identification of a tyrosine hydroxylase encoded in the parasite genome. In this study,…
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Toxoplasma gondii-altered host behaviour: clues as to mechanism of action.J. Webster, G. McConkey · 2010 · Folia Parasitologica · Not summarized yet
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Toxoplasma-induced changes in host risk behaviour are independent of parasite-derived AaaH2 tyrosine hydroxylaseC. Afonso, V. Paixão, Andreas Klaus et al. · 2017 · Scientific Reports · Not summarized yet
Abstract
Toxoplasma gondii infects a broad range of hosts and can establish chronic infections with the formation of brain cysts. Infected animals show altered risk behaviour which has been suggested to increase capture probability of hosts, and thus enhance parasite transmission. It has been proposed that the ability of Toxoplasma cysts to secrete tyrosine hydroxylase could mediate these behavioural alterations. We tested the involvement of secreted tyrosine hydroxylase, coded by the parasite AaaH2 gene, in the development of alterations in mouse behaviour, by generating an AaaH2 deletion mutant parasite strain and testing its influence on behaviour. We found that both mice infected with wild type o…
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Toxoplasma gondii infection, from predation to schizophrenia: can animal behaviour help us understand human behaviour?J. Webster, M. Kaushik, G. Bristow et al. · 2013 · Journal of Experimental Biology · Not summarized yet
Abstract
Summary We examine the role of the protozoan Toxoplasma gondii as a manipulatory parasite and question what role study of infections in its natural intermediate rodent hosts and other secondary hosts, including humans, may elucidate in terms of the epidemiology, evolution and clinical applications of infection. In particular, we focus on the potential association between T. gondii and schizophrenia. We introduce the novel term ‘T. gondii–rat manipulation–schizophrenia model’ and propose how future behavioural research on this model should be performed from a biological, clinical and ethically appropriate perspective.
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Toxoplasma-induced behavior changes - is microbial dysbiosis the missing link?E. Prandovszky, E. Severance, Victor W. Splan et al. · 2024 · Frontiers in Cellular and Infection Microbiology · Not summarized yet
Abstract
Toxoplasma gondii (T. gondii) is one of the most successful intracellular protozoa in that it can infect the majority of mammalian cell types during the acute phase of infection. Furthermore, it is able to establish a chronic infection for the host’s entire lifespan by developing an encysted parasite form, primarily in the muscles and brain of the host, to avoid the host immune system. The infection affects one third of the world population and poses an increased risk for people with a suppressed immune system. Despite the dormant characteristics of chronic T. gondii infection, there is much evidence suggesting that this infection leads to specific behavior changes in both humans and rodents…
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Parasite-altered behaviour: is the effect of Toxoplasma gondii on Rattus norvegicus specific?M. Berdoy, J. Webster, D. Macdonald · 1995 · Parasitology · Not summarized yet
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Induction of changes in human behaviour by the parasitic protozoan Toxoplasma gondiiJ. Flegr, Š. Zitková, P. Kodym et al. · 1996 · Parasitology · Not summarized yet
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Identification of Toxoplasma Gondii Tyrosine Hydroxylase (TH) Activity and Molecular Immunoprotection against ToxoplasmosisZhen-Chao Zhang, Yu-Hua Li, Haoran Li et al. · 2020 · Vaccines · Not summarized yet
Abstract
The neurotropic parasite Toxoplasma gondii (T. gondii) infection can change the behavior of rodents and cause neuropsychological symptoms in humans, which may be related to the change in neurotransmitter dopamine in the host brain caused by T. gondii infection. T. gondii tyrosine hydroxylase (TgTH) is an important factor in increasing the neurotransmitter dopamine in the host brain. In this study, the enzyme activity of TgTH catalytic substrate for dopamine production and the molecular characteristics of TgTH were identified. In order to amplify the open reading frame (ORF), the designing of the specific primers for polymerase chain reaction (PCR) was on the basis of the TgTH sequence (GenBa…
Prior work it builds on
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Toxoplasma gondii and Psychopathology: Latent Infection Is Associated with Interpersonal Sensitivity, Psychoticism, and Higher Testosterone Levels in Men, but Not in WomenJavier I. Borráz-León, M. Rantala, S. Luoto et al. · 2021 · Adaptive Human Behavior and Physiology · Not summarized yet
Abstract
Objective The ability of parasites to hijack the nervous system, manipulating the host’s physiology and behavior in ways that enhance the parasite’s fitness while damaging host fitness, is a topic of ongoing research interest in evolutionary biology, but is largely overlooked in mental health research. Nevertheless, recent evidence has shown that Toxoplasma gondii infection can change host testosterone levels and influence the development of some psychiatric disorders. Here, we tested this hypothesis in a mixed sample of 213 non-clinical subjects. Methods Participants ( n males = 108, n females = 105) provided 5 ml of blood to quantify testosterone levels and Toxoplasma gondii antibodies. Th…
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Effects of toxoplasma on human behavior.J. Flegr · 2007 · Schizophrenia bulletin · Not summarized yet
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Infection-induced extracellular vesicles evoke neuronal transcriptional and epigenetic changesE. Tedford, N. Badya, Conor Laing et al. · 2020 · bioRxiv · Not summarized yet
Abstract
Infection with the protozoan Toxoplasma gondii induces changes in neurotransmission, neuroinflammation, and behavior, yet it remains elusive how these changes come about. In this study we investigated how norepinephrine levels are altered by infection. TINEV (Toxoplasma-induced neuronal extracellular vesicles) isolated from infected noradrenergic cells down-regulated dopamine ß-hydroxylase ( DBH ) gene expression in human and rodent cells. Here we report that intracerebral injection of TINEVs into the brain is sufficient to induce DBH down-regulation and distrupt catecholaminergic signalling. Further, TINEV treatment induced hypermethylation upstream of the DBH gene. An antisense lncRNA to D…
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Sex-specific changes in gene expression and behavior induced by chronic Toxoplasma infection in mice.Jianchun Xiao, G. Kannan, L. Jones-Brando et al. · 2012 · Neuroscience · Not summarized yet
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Downregulation of the Central Noradrenergic System by Toxoplasma gondii InfectionI. Alsaady, E. Tedford, Mohammad A. Alsaad et al. · 2018 · Infection and Immunity · Not summarized yet
Abstract
Toxoplasma gondii is associated with physiological effects in the host. Dysregulation of catecholamines in the central nervous system has previously been observed in chronically infected animals. ABSTRACT Toxoplasma gondii is associated with physiological effects in the host. Dysregulation of catecholamines in the central nervous system has previously been observed in chronically infected animals. In the study described here, the noradrenergic system was found to be suppressed with decreased levels of norepinephrine (NE) in brains of infected animals and in infected human and rat neural cells in vitro. The mechanism responsible for the NE suppression was found to be downregulation of dopamin…
Papers that cite it
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From cats to cortex: T. gondii and psychosis, depression, and anxietyGabriel Andrade, Abderrahim Benlahcene, Dalia A. Bedewy · 2026 · Frontiers in Psychiatry · Not summarized yet
Abstract
This review examines whether cat ownership, via exposure to the neurotropic parasite T. gondii, contributes to vulnerability for psychotic, depressive, and anxiety symptoms. T. gondii establishes lifelong latent infection in the brain and muscle, where it can modulate dopaminergic signaling, neuroinflammation, and tryptophan–kynurenine metabolism, providing a biologically plausible pathway to altered cognition, mood, and behavior. Epidemiological and meta-analytic data indicate small-to-moderate associations between T. gondii seropositivity and schizophrenia, with more variable but suggestive links to depression and anxiety. Evidence for cat ownership as an independent risk factor is inconsi…
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Sequentially activated fluorescent probes based on a purine scaffold: enabling precise spatiotemporal monitoring of H2O2 and tyrosine hydroxylase in the brainstem NTS during spontaneous hypertension.Yang Yu, Jia Yao, Xiao-Qi Yu et al. · 2026 · In Analysis · Not summarized yet
Abstract
Spontaneous hypertension (SH) is a prevalent chronic cardiovascular disorder characterized by the synergistic elevation of hydrogen peroxide (H2O2) levels and tyrosine hydroxylase (TH) activity in the brainstem nucleus tractus solitarius (NTS). Traditional detection techniques lack the specificity and spatiotemporal resolution to monitor the dynamic interplay of these two core pathological biomarkers, hindering the in-depth exploration of SH pathogenesis. Herein, a series of novel cascade-activated fluorescent probes (PPTHs) were rationally designed and synthesized based on a purine core, which achieve specific fluorescence responses only upon sequential activation by H2O2 and TH. In vitro a…
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