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Toxoplasma gondii & Human Phenotype

Compendium of Known Effects and Ongoing Research

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Chronic Toxoplasma gondii infection induces anti-N-methyl-D-aspartate receptor autoantibodies and associated behavioral changes and neuropathology

February 12, 2018
Li, Y, Viscidi, R. P., Kannan, G., McFarland,R., Pletnikov, M. V., Severance,E. G., Yolken, R. H., Xiao, J. C.
Infection and Immunity 2018; 86: DOI: 10.1128/iai.00398-18
Click for abstract
Anti-NMDA receptor (NMDAR) autoantibodies have been postulated to play a role in the pathogenesis of NMDAR hypofunction, which contributes to the etiology of psychotic symptoms. Toxoplasma gondii is a pathogen implicated in psychiatric disorders and associated with elevation of NMDAR autoantibodies. However, it remains unclear whether parasite infection is the cause of NMDAR autoantibodies. By using mouse models, we found that NMDAR autoantibody generation had a strong temporal association with tissue cyst formation, as determined by MAGI antibody seroreactivity (r = 0.96; P < 0.0001), which is a serologic marker for the cyst burden. The presence of MAGI antibody response, but not T. gondii IgG response, was required for NMDAR autoantibody production. The pathogenic relevance of NMDAR autoantibodies to behavioral abnormalities (blunted response to amphetamine-triggered activity and decreased locomotor activity and exploration) and reduced expression of synaptic proteins (the GLUN2B subtype of NMDAR and PSD-95) has been demonstrated in infected mice. Our study suggests that NMDAR autoantibodies are specifically induced by persistent T. gondii infection and are most likely triggered by tissue cysts. NMDAR autoantibody seroreactivity may be a novel pathological hallmark of chronic toxoplasmosis, which raises questions about NMDAR hypofunction and neurodegeneration in the infected brain.

Tagged: Amphetamine, antibodies, autoantibody, behavioral abnormalities, chronic infection, Dopamine, encephalitis, expression, gondii, hos, immune-response, MAGI antibody, mice, neuropathology, nmda receptor, tissue cyst, Toxoplasma gondii

BehaviorMental health

Neurobiological studies on the relationship between toxoplasmosis and neuropsychiatric diseases

October 9, 2015 Leave a Comment
Fabiani, S., Pinto, B., Bonuccelli, U., Bruschi, F.
Journal of the Neurological Sciences 2015; 35:3-8
Click for abstract
Toxoplasma gondii is a widespread protozoan parasite infecting approximately one third of the world population. After proliferation of tachyzoites during the acute stage, the parasite forms tissue cysts in various anatomical sites including the Central Nervous tissue, and establishes a chronic infection. Clinical spectrum normally ranges from a completely asymptomatic infection to severe multi-organ involvement. Many studies have suggested T. gondii infection as a risk factor for the development of some neuropsychiatric disorders, particularly schizophrenia. During the last years, a potential link with other neurobiological diseases such as Parkinson disease and Alzheimer disease has also been suggested. This review will focus on neurobiological and epidemiological data relating infection with T. gondii to neuropsychiatric diseases. (C) 2015 Elsevier B.V. All rights reserved.

Tagged: 1st-episode schizophrenia, brain, encephalitis, expression, gondii infection, immune-response, kynurenic acid, mechanisms, neurobiology, neurological diseases, neurotransmitter pathway, risk behavior, schizophrenia spectrum disorders, seroprevalence, t. gondii

Mental health

Low titer of antibody against Toxoplasma gondii may be related to resistant to cancer

October 6, 2015 12 Comments
Seyedeh, M. S., Nahid, S., Nahid, M., Shima, D. P., Morteza, Y., Hossein, Y. D.
Journal of Cancer Research and Therapeutics 2015; 11: 305-307.
Click for abstract
Context: Toxoplasma gondii is a protozoan parasite with a world-wide distribution. However, the majority of infected cases remain symptomless. There are raising scientific evidences indicating that parasitic infections induce antitumor activity against certain types of cancers. The inhibitory effect of T. gondii on cancer growth has also been shown in cell culture and mouse model. Aims: Considering the anti-tumor effect of this parasite, in this study the relationship between low titer of antibodies against T. gondii and resistant to cancers has been investigated. Subjects and Methods: In two separate experiments, anti T. gondii antibody was estimated in 150 patients with cancer and 120 normal people. Statistical Analysis Used: Chi-square test was used for data analysis. Results: The frequency of low titer antibody against Toxoplasma gondii in cancer patients was significantly higher than the frequency of low-titer antibody against this parasite in normal people. Conclusions: Exposure to T. gondii may be related to resistance to cancer.

Tagged: antibody, cancer, cells, expression, growth, infected mice, injection, lewis lung-carcinoma, lysate antigen, organisms, parasites, Toxoplasma gondii, trypanosoma-cruzi

Physical health

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

October 29, 2014
Xiao, J., Li, Y., Prandovszky, E., Karuppagounder, S. S., Talbot, C. C., Dawson, V. L., Dawson, T. M., Yolken, R. H.
Neuroscience 2014; 268: 128-138
Click for abstract
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 (5-HT) and 5-hydroxyindoleacetic acid were documented by HPLC analysis; however, the metabolism of dopamine was decreased and 5-HT 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

Tagged: alteration in expression, darpp-32, dopamine receptor pathway, expression, host behavior, messenger-rnas, mice, microRNA-132, mouse striatum, neurons, neurotransmitter, phosphatase, Schizophrenia, strains, Toxoplasma gondii

Mental health

Possible role of Toxoplasma gondii in brain cancer through modulation of host microRNAs

October 10, 2013 31 Comments
Thirugnanam S, Rout N, Gnanasekar M.
Infectious agents and cancer 2013; 8
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Background: The obligate intracellular protozoan parasite Toxoplasma gondii infects humans and other warm-blooded animals and establishes a chronic infection in the central nervous system after invasion. Studies showing a positive correlation between anti-Toxoplasma antibodies and incidences of brain cancer have led to the notion that Toxoplasma infections increase the risk of brain cancer. However, molecular events involved in Toxoplasma induced brain cancers are not well understood. Presentation of the hypothesis: Toxoplasma gains control of host cell functions including proliferation and apoptosis by channelizing parasite proteins into the cell cytoplasm and some of the proteins are targeted to the host nucleus. Recent studies have shown that Toxoplasma is capable of manipulating host micro RNAs (miRNAs), which play a central role in post-transcriptional regulation of gene expression. Therefore, we hypothesize that Toxoplasma promotes brain carcinogenesis by altering the host miRNAome using parasitic proteins and/or miRNAs. Testing the hypothesis: The miRNA expression profiles of brain cancer specimens obtained from patients infected with Toxoplasma could be analyzed and compared with that of normal tissues as well as brain cancer tissues from Toxoplasma uninfected individuals to identify dysregulated miRNAs in Toxoplasma-driven brain cancer cells. Identified miRNAs will be further confirmed by studying cancer related miRNA profiles of the different types of brain cells before and after Toxoplasma infection using cell lines and experimental animals. Expected outcome: The miRNAs specifically associated with brain cancers that are caused by Toxoplasma infection will be identified. Implications of the hypothesis: Toxoplasma infection may promote initiation and progression of cancer by modifying the miRNAome in brain cells. If this hypothesis is true, the outcome of this research would lead to the development of novel biomarkers and therapeutic tools against Toxoplasma driven brain cancers.

Tagged: activation, biology, brain, cancer, cell apoptosis, differentiation, expression, glioblastoma, infected-cells, microarray analysis, mirna, nf-kappa-b, t. gondii, tumors

Physical health

Is Toxoplasma gondii a causal agent in migraine?

October 26, 2009
Koseoglu E, Yazar S, Koc I.
American Journal of the Medical Sciences 2009; 338: 120-122.
Click for abstract
Background: Many different tissues may be parasitized by Toxoplasma gondii, particularly, lung, heart, lymphoid organs, and the central nervous tissues. Tissue cysts of this parasite in the brain may spontaneously rupture, releasing parasites that cause antibody titers to rise. In immunocompetent subjects with acquired toxoplasmosis, the most frequent symptoms were lymphadenopathy and headache. In the neurogenic inflammation theory of the pathogenesis of migraine, the cause of initial release of ions and inflammatory agents has not been established. In this study, we aimed to investigate if T gondii infection is a possible cause of neurogenic inflammation of migraines. Methods: The anti-T gondii antibody status of 104 patients with migraine were studied and compared with those of control groups, 50 healthy subjects and 50 subjects with headache due to rhinosinusitis, by using a micro-enzyme-linked immunosorbent assay technique. Results: Forty-six (44.2%) patients with migraine, 13 (26.0%) healthy control subjects, and 12 (24%) control subjects with rhinosinusitis were positive for anti-T gondii IgG antibody. The rate of positivity in the migraine patient group was statistically different from those of the control groups (P < 0.05). Conclusions: The results show the presence of chronic Toxoplasma infection in patients with migraine. Toxoplasma infection may contribute to neurogenic inflammation as the pathogenesis of migraine, as many studies in the literature have reported that Toxoplasma infection causes biochemical and immunologic changes.

Tagged: central-nervous-system, cryptogenic epilepsy, depression, elisa, encephalitis, expression, in-vitro, migraine, neurogenic inflammation, nitric-oxide synthase, replication, Schizophrenia, Toxoplasma gondii

Physical health

Seroprevalence of Toxoplasma gondii infection in arthritis patients in eastern China

December 8, 1970
Tian, A. L., Gu, Y. L., Zhou, N., Cong, W., Li, G. X., Elsheikha, H. M., Zhu, X. Q.
Infectious Diseases of Poverty 1970; 6
Click for abstract
Background: There is accumulating evidence for an increased susceptibility to infection in patients with arthritis. We sought to understand the epidemiology of Toxoplasma gondii infection in arthritis patients in eastern China, given the paucity of data on the magnitude of T. gondii infection in these patients. Methods: Seroprevalence of T. gondii infection was assessed by enzyme-linked immunosorbent assay using a crude antigen of the parasite in 820 arthritic patients, and an equal number of healthy controls, from Qingdao and Weihai cities, eastern China. Sociodemographic, clinical and lifestyle information on the study participants were also obtained. Results: The prevalence of anti-T. gondii IgG was significantly higher in arthritic patients (18.8%) compared with 12% in healthy controls (P < 0.001). Twelve patients with arthritis had anti-T. gondii IgM antibodies - comparable with 10 control patients (1.5% vs 1.2%). Demographic factors did not significantly influence these seroprevalence frequencies. The highest T. gondii infection seropositivity rate was detected in patients with rheumatoid arthritis (24.8%), followed by reactive arthritis (23.8%), osteoarthritis (19%), infectious arthritis (18.4%) and gouty arthritis (14.8%). Seroprevalence rates of rheumatoid arthritis and reactive arthritis were significantly higher when compared with controls (P < 0.001 and P = 0.002, respectively). A significant association was detected between T. gondii infection and cats being present in the home in arthritic patients (odds ratio [OR], 1.68; 95% confidence interval [CI]: 1.24 - 2.28; P = 0.001). Conclusions: These findings are consistent with and extend previous results, providing further evidence to support a link between contact with cats and an increased risk of T. gondii infection. Our study is also the first to confirm an association between T. gondii infection and arthritis patients in China. Implications for better prevention and control of T. gondii infection in arthritis patients are discussed.

Tagged: antibodies, antitoxoplasma, arthritis, autoimmunity, Cerebral toxoplasmosis, congenital toxoplasmosis, disease, expression, oocysts, prevalence, rheumatoid-arthritis, risk factors, seroprevalence, tnf-alpha, Toxoplasma gondii

Physical health

Topics

  • Behavior 105
  • Cognitive functions 64
  • Mental health 439
  • Morphology 6
  • Motor functions 10
  • Personality 36
  • Physical health 134
  • Reproduction 36
  • Reviews 40
  • Sensory functions 3
  • Uncategorized 2

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Recent articles

  • Mortality Patterns of Toxoplasmosis and Its Comorbidities in Tanzania: A 10-Year Retrospective Hospital-Based Survey February 6, 2020
  • The role of latent toxoplasmosis in the aetiopathogenesis of schizophrenia–the risk factor or an indication of a contact with cat? February 6, 2020
  • The Association between Toxoplasma gondii Infection and Risk of Parkinson’s Disease: A Systematic Review and Meta-Analysis February 6, 2020

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