Congenital Infection of Mice with Toxoplasma gondii Induces Minimal Change in Behavior and No Change in Neurotransmitter Concentrations

Goodwin, David G.; Hrubec, Terry C.; Klein, Bradley G.; Strobl, Jeannine S.; Werre, Stephen R.; Han, Qian; Zajac, Anne M.; Lindsay, David S.

doi:10.1645/ge-3068.1

Cited by 34 publications

(19 citation statements)

References 28 publications

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“…In this experiment, chronic infections were established in 10 mice infected with a virulent Type I T. gondii strain and drug cured with sulphadiazine. Similar changes in total dopamine levels were not found in mice chronically infected with a less virulent Type III strain or in congenitally infected mice (Goodwin et al, 2012). Recently, extremely high concentrations of dopamine were found to accumulate in cyst-containing brain cells and in vitro infection was found to induce high amounts of dopamine in neural cells (Prandovszky et al, 2011) (see Fig.1).…”

Section: Proximate Changes In Dopamine During T Gondii Infectionsupporting

confidence: 65%

Toxoplasma gondii infection and behaviour – location, location, location?

McConkey

Martin

Bristow

et al. 2013

Journal of Experimental Biology

193

156

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SummaryParasite location has been proposed as an important factor in the behavioural changes observed in rodents infected with the protozoan Toxoplasma gondii. During the chronic stages of infection, encysted parasites are found in the brain but it remains unclear whether the parasite has tropism for specific brain regions. Parasite tissue cysts are found in all brain areas with some, but not all, prior studies reporting higher numbers located in the amygdala and frontal cortex. A stochastic process of parasite location does not, however, seem to explain the distinct and often subtle changes observed in rodent behaviour. One factor that could contribute to the specific changes is increased dopamine production by T. gondii. Recently, it was found that cells encysted with parasites in the brains of experimentally infected rodents have high levels of dopamine and that the parasite encodes a tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of this neurotransmitter. A mechanism is proposed that could explain the behaviour changes due to parasite regulation of dopamine. This could have important implications for T. gondii infections in humans.

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Section: Proximate Changes In Dopamine During T Gondii Infectionsupporting

confidence: 65%

Toxoplasma gondii infection and behaviour – location, location, location?

McConkey

Martin

Bristow

et al. 2013

Journal of Experimental Biology

193

156

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“…Our results are consistent with other reports that investigated dopamine and neurotransmitter levels in infected rodents. For example, Goodwin et al (36) described minimal changes observed in dopamine, norepinephrine, and serotonin concentrations in the frontal cortex and striatum of chronically infected wild-type, ⌬aah2, and ⌬aah2::AAH2 parasites in tachyzoite and bradyzoite conditions in vitro. Partial and fully formed cysts were enumerated based on staining with DBL.…”

Section: Discussionmentioning

confidence: 99%

Reassessment of the Role of Aromatic Amino Acid Hydroxylases and the Effect of Infection by Toxoplasma gondii on Host Dopamine

et al. 2015

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Toxoplasma gondii infection has been described previously to cause infected mice to lose their fear of cat urine. This behavioral manipulation has been proposed to involve alterations of host dopamine pathways due to parasite-encoded aromatic amino acid hydroxylases. Here, we report successful knockout and complementation of the aromatic amino acid hydroxylase AAH2 gene, with no observable phenotype in parasite growth or differentiation in vitro and in vivo. Additionally, expression levels of the two aromatic amino acid hydroxylases were negligible both in tachyzoites and in bradyzoites. Finally, we were unable to confirm previously described effects of parasite infection on host dopamine either in vitro or in vivo, even when AAH2 was overexpressed using the BAG1 promoter. Together, these data indicate that AAH enzymes in the parasite do not cause global or regional alterations of dopamine in the host brain, although they may affect this pathway locally. Additionally, our findings suggest alternative roles for the AHH enzymes in T. gondii, since AAH1 is essential for growth in nondopaminergic cells. The protozoan parasite Toxoplasma gondii is an obligate intracellular parasite that is capable of infecting most warmblooded animals. It is a member of the phylum Apicomplexa, which also contains Plasmodium falciparum, the causative agent of malaria. Toxoplasma gondii is one of the most widely distributed parasites in the world, both in geographic location and in the diversity of its host range (1). Its only definitive hosts are members of the genus Felis. Exclusively within enterocytes of the gut, it undergoes a sexual reproductive cycle to form environmentally resistant and infectious oocysts that are shed in cat feces (2). In all other hosts, Toxoplasma gondii infection begins as a fast-growing lytic stage called the tachyzoite. Innate and adaptive immune responses restrict the growth of tachyzoites, which can respond by differentiating into bradyzoites, a semidormant stage that exists as quiescent intracellular cysts in brain and muscle tissue. This chronic infection can persist for the lifetime of the host (3). Infections spread among incidental hosts through carnivorism, vertical transmission, and ingestion of T. gondii oocysts (4).Rodents that become infected by T. gondii exhibit an unusual behavioral response: they lose their instinctive aversion to the odor of cats and instead become mildly attracted to the scent (5-13). This behavioral manipulation appears specific to the cat (7, 8), and it has been speculated that this facilitates transmission (9). The exact mechanism of this behavioral manipulation is unknown, but parasite stimulation of host dopamine pathways in the brain has been suggested as a cause (14-16). It was observed that infection of mice by T. gondii caused a 14% increase in wholebrain dopamine levels upon establishment of chronic infection (17). Additionally, dopamine receptor antagonist drugs used for the treatment of schizophrenia block cat attraction in infected rodents (18,19). T. gondii ...

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“…32 Yet, a recent study reports no changes in monoamine content in the frontal Toxoplasma Animal Models of Cognitive Deficits cortex and striatum of congenitally infected CD-1 mice. 33 Future studies are clearly needed to further evaluate alterations in dopamine neurotransmission in infected rodents in vivo and link these changes to behavioral abnormalities, including cognitive impairment. However, it seems less likely that only dopamine changes will be able to explain the entire spectrum of behavioral responses in infected animals.…”

Section: T Gondii Effects On the Brainmentioning

confidence: 99%

Toxoplasma Gondii and Cognitive Deficits in Schizophrenia: An Animal Model Perspective

Kannan

Pletnikov

2012

Schizophrenia Bulletin

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Cognitive deficits are a core feature of schizophrenia. Epidemiological evidence indicates that microbial pathogens may contribute to cognitive impairment in patients with schizophrenia. Exposure to Toxoplasma gondii (T. gondii) has been associated with cognitive deficits in humans. However, the mechanisms whereby the parasite impacts cognition remain poorly understood. Animal models of T. gondii infection may aid in elucidating the underpinnings of cognitive dysfunction. Here, we (1) overview the literature on the association of T. gondii infection and cognitive impairment, (2) critically analyze current rodent models of cognitive deficits resulting from T. gondii infection, and (3) explore possible mechanisms whereby the parasite may affect cognitive function.

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Congenital Infection of Mice with Toxoplasma gondii Induces Minimal Change in Behavior and No Change in Neurotransmitter Concentrations

Cited by 34 publications

References 28 publications

Toxoplasma gondii infection and behaviour – location, location, location?

Toxoplasma gondii infection and behaviour – location, location, location?

Reassessment of the Role of Aromatic Amino Acid Hydroxylases and the Effect of Infection by Toxoplasma gondii on Host Dopamine

Toxoplasma Gondii and Cognitive Deficits in Schizophrenia: An Animal Model Perspective

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