Effect of 17ß-Estradiol, Progesterone, and Tamoxifen on Neurons Infected with Toxoplasma gondii In Vitro.

Toxoplasma gondii (T. gondii) is the causal agent of toxoplasmosis, which produces damage in the central nervous system (CNS). Toxoplasma-CNS interaction is critical for the development of disease symptoms. T. gondii can form cysts in the CNS; however, neurons are more resistant to this infection than astrocytes. The probable mechanism for neuron resistance is a permanent state of neurons in the interface, avoiding the replication of intracellular parasites. Steroids regulate the formation of Toxoplasma cysts in mice brains. 17ß-estradiol and progesterone also participate in the control of Toxoplasma infection in glial cells in vitro. The aim of this study was to evaluate the effects of 17ß-estradiol, progesterone, and their specific agonists-antagonists on Toxoplasma infection in neurons in vitro. Neurons cultured were pretreated for 48 h with 17ß-estradiol or progesterone at 10, 20, 40, 80, or 160 nM/mL or tamoxifen 1 µM/mL plus 17ß-estradiol at 10, 20, 40, 80, and 160 nM/mL. In other conditions, the neurons were pretreated during 48 h with 4,4',4″-(4-propyl-[1H] pyrozole-1,3,5-triyl) trisphenol or 23-bis(4-hydroxyphenyl) propionitrile at 1 nM/mL, and mifepristone 1 µM/mL plus progesterone at 10, 20, 40, 80, and 160 nM/mL. Neurons were infected with 5000 tachyzoites of the T. gondii strain RH. The effect of 17ß estradiol, progesterone, their agonists, or antagonists on Toxoplasma infection in neurons was evaluated at 24 and 48 h by immunocytochemistry. T. gondii replication was measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. 17ß-Estradiol alone or plus tamoxifen reduced infected neurons (50%) compared to the control at 48 h. Progesterone plus estradiol decreased the number of intracellular parasites at 48 h of treatment compared to the control (p < 0.001). 4,4',4″-(4-propyl-[1H] pyrozole-1,3,5-triyl) trisphenol and 23-bis(4-hydroxyphenyl) propionitrile reduced infected neurons at 48 h of treatment significantly compared to the control (p < 0.05 and p < 0.001, respectively). The Toxoplasma infection process was decreased by the effect of 17ß-estradiol alone or combined with tamoxifen or progesterone in neurons in vitro. These results suggest the essential participation of progesterone and estradiol and their classical receptors in the regulation of T. gondii neuron infection.

Toxoplasmosis Is More Frequent in Schizophrenia Patients Than in the General Population in Mexico and Is Not Associated with More Severe Course of Schizophrenia Measured with the Brief Psychiatric Rating Scale.

Toxoplasmosis is a disease, which was discovered in 1908, caused by the intracellular parasite Toxoplasma gondii. T. gondii infects neuronal, glial, and muscle cells, and chronic infections are characterized by the presence of cysts, in the brain and muscle cells, formed by bradyzoites. T. gondii is capable of synthesizing L-DOPA, a precursor of dopamine. Dopamine is a neurotransmitter that is key in the etiology of neuropsychological disorders such as schizophrenia. Previous studies have shown high levels of IgG Toxoplasma antibodies in schizophrenia patients. Many published studies show that the prevalence of toxoplasmosis is higher in schizophrenia patients. In this study, we aimed to identify the prevalence of Toxoplasma infection in patients with schizophrenia and the relationships between, sociodemographic factors and the Brief Psychiatric Rating Scale. A total of 27 schizophrenic patients were included and IgG anti-T. gondii was determined in serum samples by ELISA. The Brief Psychiatric Rating Scale, sociodemographic factors were associated with seropositivity. We found that the prevalence of Toxoplasma antibodies was 51.7%. In the Brief Psychiatric Rating Scale, statistical significant association (p = 0.024) was found in Item 13 which is related to motor retardation, however, the association turned non-significant after of correction for multiple tests or after of analyzed with a logistic regression p = 0.059, odds ratio (OR) = 2.316 with a 95% confidence interval [0.970 to 5.532]. Other association was not found between toxoplasmosis and others factors. The prevalence of toxoplasmosis on our population under study was significantly higher than that reported by general population or other group of Mexican schizophrenia patients.

Kinematic Locomotion Changes in C57BL/6 Mice Infected with Toxoplasma Strain ME49.

Chronic infection with the intracellular parasite Toxoplasma gondii produces an accumulation of cysts in the brain and muscle, causing tissue damage. The cysts in the brain motor regions affect some kinematic locomotion parameters in the host. To localize the brain cysts from Toxoplasma gondii and study the changes in kinematic locomotion in C57BL/6 mice. Female adult C57BL/6 mice were infected orally with 30 ME-49 Toxoplasma gondii cysts. An uninfected group (n = 7) and two infected groups, examined 15 and 40 days postinfection, were used for this study. To evaluate kinematic locomotion, the mice were marked with indelible ink on the iliac crest, hip, knee, ankle, and phalangeal metatarsus of the left and right hindlimbs. At least three recordings were carried out to obtain videos of the left and right hindlimbs. Mice were video recorded at 90 fps at a resolution of 640 × 480 pixels while walking freely in a transparent Plexiglass tunnel. We measured the hindlimb pendular movement and the hindlimb transfer [linear displacement] curves for each step and evaluated them statistically with Fréchet dissimilarity tests. Afterward, the mice were sacrificed, and the brain, heart, skeletal muscle, lung, liver, and kidney were obtained. The different tissues were stained with hematoxylin and eosin for analysis with optical microscopy. Topographic localization of the cysts was made using bregma coordinates for the mouse brain. The cysts were distributed in several brain regions. In one mouse, cyst accumulation occurred in the hippocampus, coinciding with an alteration in foot displacement. The step length was different among the different studied groups.

Serological study on toxoplasmosis in the Haliti-Paresí community of the Utiariti indigenous territory, Campo Novo do Parecis, Mato Grosso, Brazil.

Toxoplasma gondii is the etiological agent of toxoplasmosis, a widespread zoonosis that affects several homeothermic animals, including humans. This disease causes serious health problems, such that 10% of infected individuals develop clinical manifestations. Some studies on indigenous human populations have indicated variations in seroprevalence from 10.6% to 80.4% in such populations in different regions of Brazil and in other countries like Venezuela and Malaysia. To date, there have been no studies regarding the prevalence of anti-T. gondii antibodies in Haliti-Paresí Indians living in Campo Novo do Parecis, Mato Grosso, Brazil. Our objective here was to determine the frequency of occurrence of antibodies against this protozoon in nine Haliti-Paresí villages by correlating seroprevalence with locations and variables. Serodiagnoses were made using the indirect immunofluorescence antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA) in the Laboratory for Toxoplasmosis and Other Protozoan Diseases of IOC/Fiocruz. It was considered that samples tested positive for T. gondii infection if IgG/IgM antibodies against this protozoon were detected through serodiagnosis using either IFAT or ELISA. Among the 293 samples analyzed, 66.9% presented anti-T. gondii IgG and 3.4% presented anti-T. gondii IgM. It was observed that there were no statistically significant differences in frequency of antibody occurrence among infected individuals, based on sex, schooling or occupation/activities. However, there were statistical differences based on age and villages. The prevalence observed in this study is in agreement with values found in other studies on indigenous populations in Latin America. Like among other such populations, the Haliti-Paresí villages are located close to forests and the individuals have domestic cats as pets, are involved in hunting and farming and consume water directly from water accumulation sources. These factors might cause exposure to T. gondii tissue cysts and oocysts.

Does Toxoplasma gondii infection impact liver transplantation outcomes? A systematic review.

PURPOSE: Approximately one-third of the world's population has Toxoplasma gondii infection, and one of the main routes of transmission is organ transplantation. The aim of this study was to evaluate the impact of Toxoplasma infection on liver transplantation patients. METHODOLOGY: We searched PubMed, Lilacs, Medline, Science direct, Scielo, Ebsco, Springer, Wiley, Ovid and Google Scholar for reports published up to June 2017, and a systematic review was performed. RESULTS: Twenty cases were analysed before and after liver transplantation. Primary and reactivated infections were investigated. Before transplantation, positive IgG antibodies were the predominant serological markers in donors and recipients: 40 % (D+/R-), 20 % (D+/R+) and 20 % (D-/R+). IgM was present in only 5 % of the donors (D+/R-). In four cases, the serological markers were not specified or were negative (D?/R? or D?/R-). After transplantation, IgM anti-Toxoplasma antibodies were found in 30 % of the recipients, and in 67 % of the seronegative recipients the presence of Toxoplasma DNA or tachyzoites was reported, suggesting a primary infection. Clinical symptoms were meningitis, massive cerebral oedema, encephalitis and seizures. Treatment was administered in 70 % of the patients, and 40 % died after presenting symptoms associated with Toxoplasma infection. CONCLUSIONS: Although we review Toxoplasma infection and liver transplantation cases, problems associated with the parasite may be greater than identified. Hence, follow-up studies on Toxoplasma infection in liver transplantation patients are recommended.

The role of hormones on Toxoplasma gondii infection: a systematic review.

BACKGROUND: Toxoplasma gondii is the causal agent of toxoplasmosis in which one third of the world's population has been infected. In pregnant women, it may cause abortion and severe damage to the fetal central nervous system. During pregnancy, the prevalence of toxoplasmosis increases throughout the second and third quarter of gestation, simultaneously progesterone and 17ß-estradiol also increase. Thus, it has been suggested that these hormones can aggravate or reduce parasite reproduction. The aim of this study was reviewing the relationship between hormones and infection caused by T. gondii in several experimental animal models and humans, focused mainly on: (a) congenital transmission, (b) parasite reproduction, (c) strain virulence, (d) levels of hormone in host induced by T. gondii infection, and (e) participation of hormone receptors in T. gondii infection. Are the hormones specific modulators of T. gondii infection? A systematic review methodology was used to consult several databases (Pub Med, Lilacs, Medline, Science direct, Scielo, Ebsco, Sprinker, Wiley, and Google Scholar) dated from September, 2013 to March, 2014. RESULTS: Thirty studies were included; eight studies in humans and 22 in animals and cell cultures. In the human studies, the most studied hormones were testosterone, progesterone, prolactin, and 17ß-estradiol. Type I (RH and BK) and Type II (Prugniaud, SC, ME49, T45, P78, and T38) were the most frequent experimental strains. CONCLUSIONS: Thirty-five years have passed since the first studies regarding T. gondii infection and its relationship with hormones. This systematic review suggests that hormones modulate T. gondii infection in different animal models. However, given that data were not comparable, further studies are required to determine the mechanism of hormone action in the T. gondii infectious process.