Dopamine Stimulates Propagation of<i>Toxoplasma gondii</i>Tachyzoites in Human Fibroblast and Primary Neonatal Rat Astrocyte Cell Cultures

Strobl, Jeannine S.; Goodwin, David G.; Rzigalinski, Beverly A.; Lindsay, David S.

doi:10.1645/ge-2760.1

Cited by 34 publications

(26 citation statements)

References 30 publications

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“…These could induce miR-132 and alter downstream dopamine as dopamine signaling is now known to occur in lymphocytes (Ilani et al, 2001; Taganov et al, 2006). Since both miR-132 and dopamine are “shared” by neuronal and immune processes, the changes observed in the striatum could due to reciprocal interplay between the body and brain; (ii) dopamine was recently suggested to be a beneficial factor in Toxoplasma multiplication in primary neonatal rat astrocyte cells (Strobl et al, 2012), which may explain the specific influence of infection on dopamine signaling. Certainly, further and more extensive studies are required and will be performed to strengthen and specify the data presented in this study.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-132 dysregulation in Toxoplasma gondii infection has implications for dopamine signaling pathway

Xiao¹,

Prandovszky³

et al. 2014

Neuroscience

100

105

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Congenital toxoplasmosis and toxoplasmic encephalitis can be associated with severe neuropsychiatric symptoms. However, which host cell processes are regulated and how Toxoplasma gondii affects these changes remain unclear. MicroRNAs (miRNAs) are small noncoding RNA sequences critical to neurodevelopment and adult neuronal processes by coordinating the activity of multiple genes within biological networks. We examined the expression of over 1000 miRNAs in human neuroepithelioma cells in response to infection with Toxoplasma. MiR-132, a cyclic AMP-responsive element binding (CREB)-regulated miRNA, was the only miRNA that was substantially upregulated by all three prototype Toxoplasma strains. The increased expression of miR-132 was also documented in mice following infection with Toxoplasma. To identify cellular pathways regulated by miR-132, we performed target prediction followed by pathway enrichment analysis in the transcriptome of Toxoplasma-infected mice. This led us to identify 20 genes and dopamine receptor signaling was their strongest associated pathway. We then examined myriad aspects of the dopamine pathway in the striatum of Toxoplasma infected mice 5 days after infection. Here we report decreased expression of D1-like dopamine receptors (DRD1, DRD5), metabolizing enzyme (MAOA) and intracellular proteins associated with the transduction of dopamine-mediated signaling (DARPP-32 phosphorylation at Thr34 and Ser97). Increased concentrations of dopamine and its metabolites, serotonin and 5-hydroxyindoleacetic acid were documented by HPLC analysis; however, the metabolism of dopamine was decreased and serotonin metabolism was unchanged. Our data show that miR-132 is upregulated following infection with Toxoplasma and is associated with changes in dopamine receptor signaling. Our findings provide a possible mechanism for how the parasite contributes to the neuropathology of infection.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-132 dysregulation in Toxoplasma gondii infection has implications for dopamine signaling pathway

Xiao¹,

Prandovszky³

et al. 2014

Neuroscience

100

105

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“…It is possible that the infected cells synthesize greater amounts of this neurotransmitter. The reason why type I infection might be related to an increase in dopamine levels is not clear, but notably, dopamine was recently shown to stimulate type I strain multiplication in primary neonatal rat astrocyte cells (Strobl et al 2012). This suggests that dopamine plays a supportive role in type I infection and may explain the downregulation of DRD1.…”

Section: Discussionmentioning

confidence: 99%

Abnormalities of neurotransmitter and neuropeptide systems in human neuroepithelioma cells infected by three Toxoplasma strains

Xiao¹,

Jones‐Brando³

et al. 2013

J Neural Transm

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Since Toxoplasma gondii can establish a persistent infection in the central nervous system in humans, we studied its effects on a host's neurotransmitter and neuropeptide systems (NNS). Using microarray technology we have screened the expression of genes coding for NNS in human neuroepithelioma cells in response to representative strains of Toxoplasma to identify potential target genes. Transcripts that displayed expression levels distinct from uninfected controls were examined by RT-PCR and Western blot. Our results indicate the presence of disturbed NNS upon Toxoplasma infection and the extent of this disturbance varies considerably among the three strains. In cells infected by type I strain, three neurotransmitter systems (dopamine, glutamate and serotonin) and two neuropeptides (PROK2 and TAC1) displayed abnormalities relative to controls. Type III infection led to the change of a critical enzyme, TDO2, in the kynurenine pathway. No significant effects of type II infection were found in the NNS. These data may have implications for understanding the pathogenesis and heterogeneity of neurologic disturbances in toxoplasmosis.

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“…Research from three main areas back up our understanding that dopamine is also responsible for at least some of the changes associated with latent toxoplasmosis: (1) Genetic research showed T. gondii to have two genes encoding thyroxine hydroxylase, a rate-limiting enzyme in dopamine synthesis [37]. (2) Animal research showed changes in dopamine levels in infected mice and in brain tissues [38], [39], as well as dopamine role in observed behavioural changes [40], [41] and in production of T. gondii tachyzoites in infected tissues [42]. (3) In humans, behavioural changes associated with latent toxoplasmosis suggest differences in dopamine levels in seropositive subjects [43], [44], and research of human neurotransmitter and neuropeptide systems showed (among other alterations) significant changes in protein levels of DRD1 in cells infected with type I strain of T. gondii [45]; DRD1 is involved in negative feedback regulation of dopamine release in the brain [46].…”

Section: Introductionmentioning

confidence: 99%

Contrasting Effect of Prepulse Signals on Performance of Toxoplasma-Infected and Toxoplasma-Free Subjects in an Acoustic Reaction Times Test

2014

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BackgroundAbout 30% of people on Earth have latent toxoplasmosis. Infected subjects do not express any clinical symptoms, however, they carry dormant stages of parasite Toxoplasma for the rest of their life. This form of toxoplasmosis is mostly considered harmless, however, recent studies showed its specific effects on physiology, behaviour and its associations with various diseases, including psychiatric disorders such as schizophrenia. Individuals who suffer from schizophrenia have about 2.7 times higher prevalence of Toxoplasma-seropositivity than controls, which suggests that some traits characteristic of schizophrenic patients, including the sex difference in schizophrenia onset, decrease of grey matter density in specific brain areas and modification of prepulse inhibition of startle reaction could in fact be caused by toxoplasmosis for those patients who are Toxoplasma-seropositive.Methodology/Principal FindingsWe measured the effect of prepulse inhibition/facilitation of the startle reaction on reaction times. The students, 170 women and 66 men, were asked to react as quickly as possible to a startling acoustic signal by pressing a computer mouse button. Some of the startling signals were without the prepulse, some were 20 msec. preceded by a short (20 msec.) prepulse signal of lower intensity. Toxoplasma-seropositive subjects had longer reaction times than the controls. Acoustic prepulse shorted the reaction times in all subjects. This effect of prepulse on reaction times was stronger in male subjects and increased with the duration of infection, suggesting that it represented a cumulative effect of latent toxoplasmosis, rather than a fading out after effect of past acute toxoplasmosis.ConclusionsDifferent sensitivity of Toxoplasma-seropositive and Toxoplasma-seronegative subjects on effect of prepulses on reaction times (the toxoplasmosis-prepulse interaction) suggested, but of course did not prove, that the alternations of prepulse inhibition of startle reaction observed in schizophrenia patients probably joined the list of schizophrenia symptoms that are in fact caused by latent toxoplasmosis.

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Dopamine Stimulates Propagation ofToxoplasma gondiiTachyzoites in Human Fibroblast and Primary Neonatal Rat Astrocyte Cell Cultures

Cited by 34 publications

References 30 publications

MicroRNA-132 dysregulation in Toxoplasma gondii infection has implications for dopamine signaling pathway

MicroRNA-132 dysregulation in Toxoplasma gondii infection has implications for dopamine signaling pathway

Abnormalities of neurotransmitter and neuropeptide systems in human neuroepithelioma cells infected by three Toxoplasma strains

Contrasting Effect of Prepulse Signals on Performance of Toxoplasma-Infected and Toxoplasma-Free Subjects in an Acoustic Reaction Times Test

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