Contribution of dopamine neurotransmission in proconvulsant effect of Toxoplasma gondii infection in male mice

Epilepsy is one of the most common neurologic disorders worldwide with no distinguishable cause in 60% of patients. One‐third of world's population is infected with Toxoplasma gondii (T. gondii). This intracellular parasite has high tendency to excitable cells including neurons. We assessed sei...

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Published inJournal of neuroscience research Vol. 95; no. 10; pp. 1894 - 1905
Main Authors Babaie, Jalal, Sayyah, Mohammad, Fard‐Esfahani, Pezhman, Golkar, Majid, Gharagozli, Kourosh
Format Journal Article
LanguageEnglish
Published United States Wiley Subscription Services, Inc 01.10.2017
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Summary:Epilepsy is one of the most common neurologic disorders worldwide with no distinguishable cause in 60% of patients. One‐third of world's population is infected with Toxoplasma gondii (T. gondii). This intracellular parasite has high tendency to excitable cells including neurons. We assessed seizure susceptibility and involvement of dopaminergic system in male mice with acute and chronic T. gondii infection. Mice were infected by intraperitoneal injection of T. gondii cysts. Acute and chronic stages of infection were determined by quantification of SAG1/BAG1 transcripts and level of repetitive REP‐529 sequence in the brain of mice by real‐time PCR. Threshold of clonic seizures was measured by tail vein infusion of pentylenetetrazole. The infected mice were pretreated with D1 and D2 dopamine receptor antagonists, and seizure threshold was measured. Moreover, seizure threshold was determined after treatment of toxoplasmosis by sulfamethoxazole and trimethoprim. SAG1 level reached the maximum at week 2 after infection and then declined. The maximum level of BAG1 was observed at the week 3 and preserved till the week 8. REP‐529 was detected at first week after infection, reached maximum at the week 3 and kept at this level till the eighth week. Threshold of seizures significantly decreased in both acute and chronic phases of infection. D1 and D2 receptors antagonists inhibited proconvulsant effect of toxoplasmosis. Chemotherapy inhibited parasite growth and multiplication, and returned seizure susceptibility to the level of non‐infected mice. Dopaminergic neurotransmission participates in proconvulsant effect of T. gondii. The effect of parasite is eliminated by antibiotic therapy. © 2017 Wiley Periodicals, Inc. Acute and chronic Toxoplasma infection decrease seizure threshold in mice. D1 and D2 dopamine receptors play role in proconvulsant effect of toxoplasmosis.
Bibliography:This work was supported by grant No. 751 from Pasteur Institute of Iran
Toxoplasma gondii
on the brain excitability is not a permanent and irreversible event; rather it is reversed by antibiotic therapy.
infection in the mouse brain by measuring the parasite load and the level of specific parasite phenotypes in each phase. Then, we showed correlation of the acute and chronic phases of infection with increased seizure susceptibility of mice. The major finding of the study is involvement of dopaminergic system in the proconvulsant effect of toxoplasmosis, which is reported for the first time. Moreover, the impact of
SIGNIFICANCE We differentiated the chronic and acute phases of
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ISSN:0360-4012
1097-4547
DOI:10.1002/jnr.24036