Mahmoudvand Hossein, Ziaali Naser, Aghaei Iraj, Sheibani Vahid, Shojaee Saeideh, Keshavarz Hossein, Shabani Mohammad
1 Department of Medical Parasitology and Mycology, Lorestan University of Medical Sciences , Khorramabad, Iran.
Pathog Glob Health. 2015;109(8):369-76. doi: 10.1080/20477724.2015.1117742.
There are conflicting reports concerning the association of Toxoplasma gondii infection with increased risk of mental disorders. This investigation will provide a good understanding about defining the possible association between T. gondii exposure and risk of anxiety and cognitive alterations. Besides, a secondary objective of this study was to determine the effect of pioglitazone administration on the possible alterations induced by T. gondii exposure. Male BALB/c mice were used for this study. The animal model of Toxoplasma infection was established by the intraperitoneal inoculation of 20-25 tissue cysts from Tehran strain of T. gondii. Pioglitazone (20 mg/kg, i.p.1/day) was administered to the animals for 2 weeks before behavioural tests. Behavioural tests including open-field, elevated plus-maze and passive avoidance learning were evaluated in the groups. Since cytokines were implicated as a contributing factor for mood disorders, the mRNA levels of TNF-α, IL-1β, IL-6 as well as inducible nitric oxide synthase (iNOs) were examined by real-time PCR. Findings demonstrated that T. gondii caused anxiety-like symptoms and impaired cognitive functions of the infected BALB/c mice, whereas pioglitazone, a peroxisome proliferator-activated receptor agonist, showed a promising effect against the cognitive impairments induced by Toxoplasma infection. The results also revealed that the mRNA levels of the aforementioned cytokines were significantly (p < 0.05) increased in the infected mice compared to the uninfected BALB/c ones. Pioglitazone can be offered as a potential neuroprotective agent in the treatment of patients with T. gondii infection that manifests anxiety and cognitive impairments; however, further studies are needed to clarify the exact mechanisms.
关于弓形虫感染与精神障碍风险增加之间的关联,存在相互矛盾的报道。本研究将有助于深入了解弓形虫暴露与焦虑及认知改变风险之间的可能关联。此外,本研究的第二个目的是确定吡格列酮给药对弓形虫暴露所致可能改变的影响。本研究使用雄性BALB/c小鼠。通过腹腔接种来自德黑兰株弓形虫的20 - 25个组织包囊建立弓形虫感染动物模型。在行为测试前2周,给动物腹腔注射吡格列酮(20 mg/kg,每天1次)。对各组动物进行包括旷场试验、高架十字迷宫试验和被动回避学习试验在内的行为测试。由于细胞因子被认为是情绪障碍的一个促成因素,通过实时聚合酶链反应检测肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)以及诱导型一氧化氮合酶(iNOs)的mRNA水平。研究结果表明,弓形虫导致受感染的BALB/c小鼠出现焦虑样症状并损害其认知功能,而过氧化物酶体增殖物激活受体激动剂吡格列酮对弓形虫感染所致的认知损害显示出有前景的治疗效果。结果还显示,与未感染的BALB/c小鼠相比,感染小鼠中上述细胞因子的mRNA水平显著升高(p < 0.05)。吡格列酮可作为一种潜在的神经保护剂,用于治疗表现出焦虑和认知损害的弓形虫感染患者;然而,需要进一步研究以阐明确切机制。