BACKGROUND/PURPOSE Toxocariasis is a worldwide parasitic zoonosis and mainly caused by Toxocara canis. Humans can be infected by accidental ingestion of T. canis embryonated ova through contacting with contaminated food, water, or encapsulated larvae in paratenic hosts' viscera or meat. Since humans are the paratenic host of T. canis, the wandering and neuroinvasive larvae can cause mechanical tissue damage and the excretory-secretory antigens (TcES Ag) might induce neuroinflammatory responses in the brain. Human cerebral toxocariasis (CT) has been reported to cause several neurological symptoms and may develop into neurodegenerative diseases. However, the roles of astrocytes involved in the pathogenesis of CT remained largely unclear. METHODS This study intended to investigate the cytotoxic effects of TcES Ag on astrocytes as assessed by apoptosis and autophagy expression. RESULTS Our results showed TcES Ag treatment reduced cell viability and caused morphological changes. Expressions of autophagy associated proteins including Beclin 1, phosphor-mTOR and LC3-Ⅱ were not significantly changed; however, p62 as well as the cell survival protein, mTOR, was concomitantly decreased in TcES Ag treatment. Significantly accelerated cleaved caspase-3 and cytochrome c expression as well as enhanced caspase-9 and caspase-8 activation were found in astrocytes with TcES Ag treatment. Caspase-3 activity and apoptotic cells numbers were also increased as detected by fluorescence microscopy. CONCLUSION We concluded that TcES Ag may trigger astrocytes apoptosis predominantly through intrinsic and extrinsic pathways rather autophagy, revealing a novel role of astrocytes in the pathogenesis of CT.

中文翻译：

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在犬弓形虫幼虫排泄分泌抗原引起的星形胶质细胞中，主要是大量的凋亡而不是自噬。

背景/目的弓形虫病是一种世界范围的寄生虫人畜共患病，主要由犬弓形虫引起。通过接触受污染的食物，水或囊状幼虫内脏或肉类中包裹的幼虫，可意外摄入犬蒂莫氏菌胚卵，从而感染人类。由于人类是犬圆弧菌的寄生虫宿主，所以游荡和神经侵袭性幼虫会引起机械组织损伤，排泄-分泌抗原（TcES Ag）可能会在大脑中诱发神经炎症反应。据报道，人脑弓形虫病（CT）会引起多种神经系统症状，并可能发展成神经退行性疾病。然而，星形胶质细胞在CT发病机制中的作用仍不清楚。方法本研究旨在研究TcES Ag对星形胶质细胞的细胞毒性作用，并通过凋亡和自噬表达对其进行评估。结果我们的结果表明TcES Ag处理降低了细胞活力并引起了形态变化。自噬相关蛋白包括Beclin 1，phosphor-mTOR和LC3-Ⅱ的表达未见明显变化。然而，在TcES Ag处理中，p62以及细胞存活蛋白mTOR同时降低。在用TcES Ag处理的星形胶质细胞中发现了明显加速的裂解的caspase-3和细胞色素c表达以及增强的caspase-9和caspase-8活化。通过荧光显微镜检测，Caspase-3活性和凋亡细胞数也增加。