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首页> 外文期刊>International journal of molecular medicine >Sulindac attenuates valproic acid-induced oxidative stress levels in primary cultured cortical neurons and ameliorates repetitive/stereotypic-like movement disorders in Wistar rats prenatally exposed to valproic acid
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Sulindac attenuates valproic acid-induced oxidative stress levels in primary cultured cortical neurons and ameliorates repetitive/stereotypic-like movement disorders in Wistar rats prenatally exposed to valproic acid

机译：舒林酸可减轻丙戊酸诱导的原代培养皮层神经元中氧化应激水平，并改善出生前暴露于丙戊酸的Wistar大鼠的重复/定型样运动障碍

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Accumulating evidence suggests that anti-inflammatory agents and antioxidants have neuroprotective properties and may be beneficial in the treatment of neurodevelopental disorders, such as autism. In the present study, the possible neuroprotective properties of sulindac, a non-steroidal anti-inflammatory drug (NSAID), were investigated in?vitro using cultured cortical neurons with valproic acid (VPA)-induced neurotoxicity, as well as in?vivo through the behavioral analysis of rats prenatally exposed to VPA as a model of autism. VPA induced 4-hydroxynonenal (4-HNE) expression, reactive oxygen species (ROS) generation and decreased cell viability in primary cultured cortical neurons established from timed-pregnant (embryonic day?18) Wistar rat pups. However, co-incubation of the neurons with VPA and sulindac reduced oxidative stress and increased cell viability. The rats were administered an intraperitoneal injection with one of the following: VPA, sulindac, VPA and sulindac, or physiological saline, and their offspring were subjected to the open field test. During the test trials, repetitive/stereotypic-like movements for each rat were recorded and analyzed. The results revealed that treatment with both sulindac and VPA reduced the VPA-induced repetitive/stereotypic-like activity and the sulindac and VPA-treated animals responded better in the open field test compared to the VPA-treated animals. The results from the present study demonstrate that the antioxidant properties of sulindac may prove to be beneficial in the treatment of autism, suggesting that the upregulation of the Wnt/β-catenin signaling pathway disrupts oxidative homeostasis and facilitates susceptibility to autism.
机译：越来越多的证据表明，抗炎药和抗氧化剂具有神经保护特性，可能对自闭症等神经发育疾病的治疗有益。在本研究中，使用培养的皮层神经元与丙戊酸（VPA）诱导的神经毒性，以及通过体外在体外的体外培养，研究了舒林酸（一种非甾体类抗炎药（NSAID））的可能的神经保护特性。作为自闭症模型的产前暴露于VPA的大鼠的行为分析。 VPA诱导Wistar大鼠幼犬建立的原代培养皮层神经元中的4-羟壬醛（4-HNE）表达，活性氧（ROS）生成和细胞活力降低。但是，将神经元与VPA和舒林酸共同孵育可减少氧化应激并增加细胞活力。给大鼠腹膜内注射以下药物之一：VPA，舒林酸，VPA和舒林酸或生理盐水，并对它们的后代进行野外试验。在测试试验中，记录并分析了每只大鼠的重复性/定型运动。结果表明，舒林酸和VPA均降低了VPA诱导的重复/定型样活性，与VPA处理的动物相比，舒林酸和VPA处理的动物在野外试验中的反应更好。本研究的结果表明，舒林酸的抗氧化特性可能被证明对自闭症的治疗有益，这表明Wnt /β-catenin信号通路的上调会破坏氧化稳态并促进对自闭症的易感性。

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