Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, Jilin, China.
Parasite Immunol. 2021 Dec;43(12):e12893. doi: 10.1111/pim.12893. Epub 2021 Oct 20.
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.
刚地弓形虫（Toxoplasma gondii，T. gondii）是一种神经嗜性的原生动物寄生虫，可导致精神和行为障碍。本研究旨在阐明舍曲林（SERT）对刚地弓形虫感染诱导的抑郁样行为的影响及其潜在的分子机制。本研究通过感染刚地弓形虫 RH 株建立了小鼠模型和小胶质细胞系（BV2 细胞）模型。在体内和体外实验中，研究了 SERT 在抑制小鼠大脑和 BV2 细胞中由刚地弓形虫感染引起的抑郁样行为和细胞扰动的潜在分子机制。SERT 的给药显著改善了刚地弓形虫感染小鼠的抑郁样行为。此外，SERT 抑制刚地弓形虫的增殖。SERT 治疗显著抑制小胶质细胞的激活，并通过下调肿瘤坏死因子受体 1/核因子-κB 信号通路降低肿瘤坏死因子-α和干扰素-γ等促炎细胞因子的水平，从而改善刚地弓形虫感染诱导的抑郁样行为。本研究深入了解了 SERT 对抗刚地弓形虫感染诱导的抑郁样行为的新作用的潜在分子机制。
