Investigating the effect of risperidone drug in inhibiting the proliferation of Toxoplasma gondii parasite in the mice brain

Individuals infected with Toxoplasma gondii (T. gondii) are prone to psycho-behavioural disorders, most notably schizophrenia and bipolar disorder. Aantipsychotic and mood-stabilizing drugs inhibited proliferation of T. gondii tachyzoites in vitro. However, results are controversial for animals which has treated with such drugs. In this study, an absolute quantitative real-time PCR (qPCR) was applied to accurately quantify the transcription level of BAG1 and SAG1 (a specific protein of T. gondii bradyzoite and tachyzoite, respectively) and copy number of REP529 DNA (a repetitive DNA fragment of the parasite) in brains of chronically infected NMRI mice treated by a neuroleptic drug; risperidone. The results showed treatment with this drug significantly inhibited the chronic infection and decreased BAG1, SAG1 and REP529 copy numbers in mice brains (P < 0.0001), comparable to cotrimoxazole, the standard drug for the treatment of Toxoplasma infection (P > 0.05). Moreover, brain TNF-α expression was significantly reduced upon treatment (P < 0.0001), comparable to cotrimoxazole (P > 0.05). Histological examination of mice brains showed marked reduction in cyst establishment, as well as in perivascular infiltration of lymphocytes, glial nodules, and encephalitis in the animals administered with the tested drug, to the same level as the cotrimoxazole group. The results provided direct evidence for the efficacy of this antipsychotic drug against chronic Toxoplasma infection. These results might help modulate therapeutic regimens for schizophrenia patients and design more effective anti-Toxoplasma drugs.