New role of sertraline against Toxoplasma gondii-induced depression-like behaviours in mice

Toxoplasma gondii ( T . gondii ) is a neurotropic protozoan parasite, which can cause mental and behavioural disorders. The present study aimed to elucidate the effects and underlying molecular mechanisms of sertraline (SERT) on T . gondii -induced depression-like behaviours. In the present study, a mouse model and a microglial cell line (BV2 cells) model were established by infecting with the T . gondii RH strain. In in vivo and in vitro experiments, the underlying molecular mechanisms of SERT in inhibiting depression-like behaviours and cellular perturbations caused by T . gondii infection were investigated in the mouse brain and BV2 cells. The administration of SERT significantly ameliorated depression-like behaviours in T . gondii -infected mice. Furthermore, SERT inhibited T . gondii proliferation. Treatment with SERT significantly inhibited the activation of microglia and decreased levels of pro-inflammatory cytokines such as tumour necrosis factor-alpha, and interferon-gamma, by down-regulating tumour necrosis factor receptor 1/nuclear factor-kappa B signalling pathway, thereby ameliorating the depression-like behaviours induced by T . gondii infection. Our study provides insight into the underlying molecular mechanisms of the newly discovered role of SERT against T . gondii -induced depression-like behaviours.