Valproic acid inhibits chronic
Toxoplasma
infection and associated brain inflammation in mice
Individuals infected with Toxoplasma gondii ( T. gondii ) are prone to psycho-behavioral disorders, most notably schizophrenia and bipolar. Valproic acid reportedly inhibited the proliferation of T. gondii tachyzoites in vitro. However, animals treated with the drug neither lived longer during acute infection nor had fewer brain cysts upon chronic infection. In this study, a quantitative real-time PCR (qPCR) method was applied to quantify copy numbers of BAG1 (a bradyzoite-specific protein), REP529 DNA (a repetitive DNA fragment of the parasite), and SAG1 (a highly expressed tachyzoite-specific surface protein) in brains of chronically infected mice treated by valproic acid. The treatment inhibited the infection and decreased BAG1, SAG1, and REP529 copy numbers in mice brains ( P < 0.0001 ), comparable to Trimethoprim/Sulfamethoxazole (TMP/SMZ), the common medication for Toxoplasmosis treatment. Moreover, valproic acid decreased brain TNF-α expression ( P < 0.0001 ), comparable to TMP/SMZ. Histological examination of mice brains showed a marked reduction in cyst establishment, perivascular infiltration of lymphocytes, and glial nodules to the same level as the TMP/SMZ group. Our results provide direct evidence for the efficacy of valproic acid, a mood-stabilizing and antipsychotic drug against chronic Toxoplasma infection. These results might help modulate therapeutic regimens for neuropsychiatric patients and design more effective anti- Toxoplasma drugs.