nitric-oxide synthase – Toxoplasma gondii & Human Phenotype

Combined Toxoplasma gondii seropositivity and high blood kynurenine – Linked with nonfatal suicidal self-directed violence in patients with schizophrenia

October 3, 2016
Okusaga, O., Duncan, E., Langenberg, P., Brundin, L., Fuchs, D., Groer, M. W., Giegling, I., Stearns-Yoder, K. A., Hartmann, A. M., Konte, B., Friedl, M., Brenner, L. A., Lowry, C. A., Rujescu, D., Postolache, T. T.
Journal of Psychiatric Research 2016; 72: 74-81

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Possible link between Toxoplasma gondii and the anosmia associated with neurodegenerative diseases

October 10, 2014
Prandota J.
American Journal of Alzheimers Disease and Other Dementias 2014; 29: 205-214

The diagnosis of a personality disorder increases the likelihood for seropositivity to Toxoplasma gondii in psychiatric patients

October 19, 2010
Hinze-Selch, D., Daubener, W., Erdag, S., Wilms, S.
Folia Parasitol (Praha) 2010; 57: 129-135

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Neuropathological changes and clinical features of autism spectrum disorder participants are similar to that reported in congenital and chronic cerebral toxoplasmosis in humans and mice

October 19, 2010
Prandota J.
Research in Autism Spectrum Disorders 2010; 4: 103-118.

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Anatomic, histopathologic, and MRI/SPET studies of autistic spectrum disorders (ASD) patients' brains confirm existence of very early developmental deficits. In congenital and chronic murine toxoplasmosis several cerebral anomalies also have been reported, and worldwide, approximately two billion people are chronically infected with T. gondii with largely yet unknown consequences. The aim of the study was therefore to compare brain abnormalities in ASD patients with those found in mice with cerebral toxoplasmosis (CT) because this may help in understanding pathophysiology of ASD. Data from available published studies were analyzed to compare postmortem pathologic changes found in the brains of ASD patients with those of mice developed after intraperitoneal T.gondii infection. Patients with ASD had the following brain abnormalities: active neuroinflammatory process notably in cerebellum, microglial nodules, accumulation of perivascular macrophages, decreased number and size of Purkinje cells in cerebellar nuclei and inferior olive, hypoperfusion of brain. Mice with congenital toxoplasmosis also had persistent neuroinflammation and ventricular enlargement, periventricular edema, meningeal and perivascular inflammation, and focal loss of Purkinje and granule cells. In murine acquired CT, the brain anomalies included: ventricular dilatation probably reflecting loss of brain parenchyma; perivascular inflammation particularly in hippocampus, and periaqueductal/periventricular areas, Purkinje cell layer markedly disfigured with focal loss of cells: perivascular cuffing by mononuclear cells and localized microglial/inflammatory nodules. Infection of mice with different strains of T. gondii resulted in distinctive neuropathological changes and various stadium of maturity of cysts and the parasite itself, which is in line with the diversity of the autistic phenotypes. Also, the abnormalities in behavior and clinical features associated with autism resembled that reported in chronic latent toxoplasmosis in humans and rodents. All these similarities suggest that T gondii should be regarded as an important infectious factor that may trigger development of ASD and some other neurodegenerative diseases, such as obsessive-compulsive and attention-deficit/hyperactivity disorders, and cryptogenic epilepsy. Thus, all these patients should be tested for T. gondii infection. (C) 2009 Elsevier Ltd. All rights reserved.

Autism spectrum disorders may be due to cerebral toxoplasmosis associated with chronic neuroinflammation causing persistent hypercytokinemia that resulted in an increased lipid peroxidation, oxidative stress, and depressed metabolism of endogenous and exogenous substances

October 19, 2010
Prandota J.
Research in Autism Spectrum Disorders 2010; 4: 119-155

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Worldwide, approximately 2 billion people are chronically infected with Toxoplasma gondii with largely yet unknown consequences. Patients with autism spectrum disorders (ASD) similarly as mice with chronic toxoplasmosis have persistent neuroinflammation, hypercytokinemia with hypermetabolism associated with enhanced lipid peroxidation, and extreme changes in the weight resulting in obesity or wasting. Data presented in this review suggest that environmental triggering factors such as pregnancy, viral/bacterial infections, vaccinations, medications, and other substances caused reactivation of latent cerebral toxoplasmosis because of changes in intensity of latent central nervous system T. gondii infection/inflammation and finally resulted in development of ASD. Examples of such environmental factors together with their respective biomarker abnormalities are: pregnancy (increased NO, IL-1 beta, TNF-alpha, IL-6, IL-10, prolactin: decreased IFN-gamma, IL-12), neuroborreliosis (increased IL-1 beta, sIL-1R2, TNF-alpha, IFN-gamma, IL-6, IL-10, IL-12, IL-18, transforming growth factor-beta 1 (TGF-beta 1)), vital infections (increased IL-1 beta, IL-6, IL-8, TNF-alpha, IFN-gamma/alpha/beta,TGF-beta 1), thimerosal (increased IL-5, IL-13; decreased IFN-gamma,TNF-alpha,IL-6, IL-12p70, NOS), and valproic acid (increased NO, reactive oxygen species; decreased TNF-alpha, IL-6, IFN-gamma). The imbalances in pro- and antiinflammatory processes could markedly hinder [lost defense mechanisms important for immune control of the parasite, such as the production of NO, cytokines, and reactive oxygen/nitrogen species, tryptophan degradation by indoleamine 2,3-dioxygenase and/or tryptophan 2,3-dioxygenase, limitation of the availability of intracellular iron to T gondii, and the mechanisms mediated by an IFN-gamma responsive gene family. These fluctuations could result in a recurrent profuse multiplication of T. gondii in the brain associated with persistent neuroinflammation, chronic overproduction of pro- and antiinflammatory cytokines, and NO causing increased oxidative stress, and significantly depressed activity of several enzymes including cytochrome P450 monooxygenase family responsible for metabolism of physiological substrates and xenobiotics, such as steroids, fatty acids, prostaglandins, drugs, pollutants, and carcinogens, finally leading to development of ASD. This reasoning may be supported by such abnormal metabolic events as: (1) patients with ASD have significantly decreased melatonin levels caused by marked deficit in acetylserotonin methyltransferase activity, possibly resulting from maternal and/or fetal/postnatal overproduction of NO, characteristic for this clinical entity; (2) thimerosal inhibited both insulin-like growth factor-1- and dopamine-stimulated methylation reactions, and depressed methionine synthase activity, the metabolic events important for promoting normal neurodevelopment; (3) valproic acid, a strong histone deacetylase inhibitor, have potent anti-T. gondii activity. Thus, patients with ASD should be tested for T. gondii infection. (C) 2009 Elsevier Ltd. All rights reserved

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.

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The importance of Toxoplasma gondii infection in diseases presenting with headaches. Headaches and aseptic meningitis may be manifestations of the Jarisch-Herxheimer reaction

October 26, 2009
Prandota J.
International Journal of Neuroscience 2009; 119: 2144-2182.

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A controlled prospective study of Toxoplasma gondii infection in individuals with schizophrenia: Beyond seroprevalence

October 27, 2007
Hinze-Selch, D., Daubener, W., Eggert, L., Erdag, S., Stoltenberg, R., Wilms, S.
Schizophrenia Bulletin 2007; 33: 782-788.

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Schizophrenia susceptibility genes directly implicated in the life cycles of pathogens: Cytomegalovirus, influenza, herpes simplex, rubella, and Toxoplasma gondii.

October 30, 2006
Carter CJ.
Schizophrenia Bulletin 2006; 35: 1163-1182

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