Effect of parasitic infection on dopamine biosynthesis in dopaminergic cells

Martin, Heather L.; Alsaady, Isra; Howell, Gareth; Prandovszky, Emese; Peers, Chris; Robinson, Philip A.; McConkey, Glenn A.

doi:10.1016/j.neuroscience.2015.08.005

Cited by 70 publications

(92 citation statements)

References 50 publications

(78 reference statements)

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“…33 Improvement of parkinsonism in an AIDS patient with cerebral toxoplasmosis was achieved after anti-T. gondii and antiretroviral therapies. 34 Infection with T. gondii has been associated with elevated levels of dopamine within dopaminergic cells, 12 whereas an important feature of Parkinson's disease is the loss of dopamine-producing neurons. 35 However, the interaction of T. gondii and neurons in patients with Parkinson's disease is largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, infection with T. gondii may increase the production of dopamine in the brain. 12 In addition, information about the presence of obesity, dyslipidaemia, diabetes mellitus, arterial hypertension, smoking, diarrhoea, nausea and/or vomiting was obtained from each patient. Antiparkinsonian medication was also registered and included the use of levodopa, carbidopa, pramipexole, trihexyphenidyl, biperiden, amantadine, rasagiline, selegiline, azilect, rotigotine and bromocriptine.…”

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

“…It therefore raises the question whether infection with T. gondii may lead to Parkinson's disease. On the other hand, infection with T. gondii may increase the production of dopamine in the brain 12. Therefore, it also raises the question whether Parkinson’s disease could be negatively associated with infection with T. gondii .…”

Section: Introductionmentioning

confidence: 99%

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Toxoplasma gondiiexposure and Parkinson's disease: a case–control study

et al. 2017

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ObjectivesTo determine the association between Toxoplasma gondii infection and Parkinson's disease and to investigate whether T. gondii seropositivity is associated with the general characteristics of patients with Parkinson's disease.DesignCase–control study.SettingCases and controls were enrolled in Durango City, Mexico.Participants65 patients with Parkinson's disease and 195 age- and gender-matched control subjects without Parkinson's disease.Primary and secondary outcome measuresSerum samples of participants were analysed for anti-T. gondii IgG and IgM antibodies by commercially available enzyme-linked immunoassays. Prevalence of T. gondii DNA was determined in seropositive subjects using PCR. The association between clinical data and infection was examined by bivariate analysis.ResultsAnti-T. gondii IgG antibodies were found in 6/65 cases (9.2%) and in 21/195 controls (10.8%) (OR 0.84; 95% CI 0.32 to 2.18; p=0.81). The frequency of high (>150 IU/mL) antibody levels was similar among cases and controls (p=0.34). None of the anti-T. gondii IgG positive cases and four of the anti-T. gondii IgG positive controls had anti-T. gondii IgM antibodies (p=0.54). The prevalence of T. gondii DNA was comparable in seropositive cases and controls (16.7% and 25%, respectively; p=1.0). Seroprevalence of T. gondii infection was associated with a young age onset of disease (p=0.03), high Unified Parkinson Disease Rating Scale scores (p=0.04) and depression (p=0.02). Seropositivity to T. gondii infection was lower in patients treated with pramipexole than in patients without this treatment (p=0.01). However, none of the associations remained significant after Bonferroni correction.ConclusionsThe results do not support an association between T. gondii infection and Parkinson's disease. However, T. gondii infection might have an influence on certain symptoms of Parkinson's disease. Further research to elucidate the role of T. gondii exposure on Parkinson's disease is warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

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Toxoplasma gondiiexposure and Parkinson's disease: a case–control study

et al. 2017

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“…Infection did not alter levels of host tyrosine hydroxylase, DOPA decarboxylase (DDC) or the vesicular monoamine transporter (VMAT) in catecholaminergic cells, although DDC was observed in the parasitophorous vacuole in vitro and within tissue cysts in vivo [68]. Catecholamine dysregulation may also be affected by disruption of catabolism of dopamine (e.g.…”

Section: Neurotransmitter Changesmentioning

confidence: 99%

Neurophysiological Changes Induced by Chronic <em>Toxoplasma gondii</em> Infection

Tedford

McConkey

2017

Preprint

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Although the parasite Toxoplasma gondii is one of the most pervasive neurotropic pathogens in the world, the host-parasite interactions during CNS infection and consequences of neurological infection are just beginning to be unraveled. The chronic stages of infection have been considered dormant, although several studies have found correlations of infection with an array of host behavioral changes. These may facilitate parasite transmission and impact neurological diseases. During infection, in addition to the presence of the parasites within neurons, hostmediated neuroimmune and hormonal responses to infection are also present. T. gondii induces numerous changes to host neurons during infection and globally alters host neurological signaling pathways, as discussed in this review. Understanding the neurophysiological changes in the host brain is imperative to understanding the parasitic mechanisms and to delineate the effects of this single-celled parasite on health and its contribution to neurological disease.

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“…However, an increase in dopamine with no modification of cellular tyrosine hydroxylase was demonstrated in vitro after parasitization of a rat pheochromocytoma cell line (PC12) and in vivo after the parasitization of mouse brains. This dopamine synthesis is attributable to the additional activity of the aromatic amino acid hydroxylase, which is encoded by two T. gondii genes [116] and has homologous activities to those of mammalian tyrosine hydroxylase, associated with the entry of cellular DDC enzymes into parasitophorous vacuoles (compartments formed by the parasite to invade the cell) and into tissue cysts (the protozoan encodes no enzyme with DDC activity) [114,117]. Experiments in cell cultures have demonstrated that dopamine increases the replication of T. gondii tachyzoites [118].…”

Section: The Importance Of Dopamine and Other Neurotransmittersmentioning

confidence: 99%

Toxoplasma gondii and Schizophrenia: A Relationship That Is Not Ruled Out

Sorlózano-Puerto¹,

Gutiérrez‐Fernández²

2016

Schizophrenia Treatment - The New Facets

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Over recent years, it has been proposed that some diseases of unknown origin, such as schizophrenia, may be caused by persistent chronic infections coupled with a genetic component and may be perpetuated by the immune system. This hypothesis is supported by epidemiological and biological evidence on the exposure of schizophrenics to infectious diseases during prenatal or postnatal periods, including Toxoplasma gondii, chlamydia, human herpes virus, human endogenous retroviruses, parvovirus B19, mumps, and flu viruses. This growing list of microbes will undoubtedly continue to increase in the future. Linking infection to schizophrenia is a complex challenge that requires further experimental and epidemiological research. T. gondii is the infectious agent that has most frequently been related to neuropsychiatric disorders, including schizophrenia, and it is considered to represent a highly useful model to analyze the influence of a microorganism on human behavior and the development of psychiatric disease. It may also help to detect patient subpopulations susceptible to treatment with specific antimicrobials by improving definition of the differential phenotype of the disease, and it offers the possibility of a preventive approach.

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Effect of parasitic infection on dopamine biosynthesis in dopaminergic cells

Abstract: Graphical abstract

Cited by 70 publications

References 50 publications

Toxoplasma gondiiexposure and Parkinson's disease: a case–control study

Toxoplasma gondiiexposure and Parkinson's disease: a case–control study

Neurophysiological Changes Induced by Chronic <em>Toxoplasma gondii</em> Infection

Toxoplasma gondii and Schizophrenia: A Relationship That Is Not Ruled Out

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