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The neuroprotective effects of stimulation of NMDA receptors against POX-induced neurotoxicity in hippocampal cultured neurons; a morphometric study
Molecular & Cellular Toxicology ( IF 1.1 ) Pub Date : 2020-06-29 , DOI: 10.1007/s13273-020-00091-9
Farideh Bahrami , Zahra Bahari , Reihaneh Abolghasemi , Lida Golmanesh , Gholam Hossein Meftahi

Background

Organophosphorus agents are potent neurotoxins that widely used as insecticides and also as poison in warfare. In the current study, we examined the neuroprotective role of NMDA receptors in Paraoxon (POX)-induced neurotoxicity of hippocampal cultured neurons.

Objective

Hippocampal neurons were isolated from the brains of neonatal rats. The cells treated with POX (100 µM) for 48 h or NMDA (NMDA receptor agonist, 100 µM) for 1 h or MK801 (NMDA receptor antagonist, 1 µM) for 15 min before the NMDA and POX treatment. The colorimetric MTS method was used for cell survival assay. The immunocytochemistry and scanning electron microscopy were done for the morphometric study and total neurotic length calculations. Additionally, the activity of the caspase-3 enzyme was determined.

Result

The present results demonstrated that POX significantly reduces the viability of cells, cell number, length of neurites, and also the surface area of neurons. We also show that POX increased the activity of the Caspase3 enzyme. Additionally, the application of NMDA significantly increased the viability of cells, cell number, and the surface area of neurons as compared with the POX group. Furthermore, pretreatment of cells with NMDA significantly decreased the activity of the Caspase3 enzyme as compared with the POX group. Application of MK801 significantly decreased cell viability, cell number, TNL, and activity of Caspase3 enzyme as compared with the control group.

Conclusion

The present study indicated that NMDA treatment has neuroprotective effects on hippocampal neurons following exposure to POX. It seems that these protective effects mediated by decrease the activity of caspase3. Additionally, pretreatment of cells with MK801 has toxicity effects on hippocampal neurons.



中文翻译:

刺激NMDA受体对POX诱导的海马培养神经元神经毒性的神经保护作用;形态计量学

背景

有机磷试剂是有效的神经毒素,广泛用作杀虫剂和战争中的毒物。在当前的研究中,我们检查了NMDA受体在对氧磷(POX)诱导的海马培养的神经元神经毒性中的神经保护作用。

目的

从新生大鼠的大脑中分离出海马神经元。在NMDA和POX处理之前,用POX(100 µM)处理48小时或NMDA(NMDA受体激动剂,100 µM)处理1 h或MK801(NMDA受体拮抗剂,1 µM)处理15分钟的细胞。比色MTS方法用于细胞存活测定。进行了免疫细胞化学和扫描电子显微镜以进行形态学研究和总神经长计算。另外,确定了胱天蛋白酶3酶的活性。

结果

目前的结果表明,POX显着降低了细胞的活力,细胞数量,神经突的长度以及神经元的表面积。我们还显示,POX增加了Caspase3酶的活性。此外,与POX组相比,NMDA的应用显着增加了细胞的活力,细胞数量和神经元的表面积。此外,与POX组相比,用NMDA预处理细胞会显着降低Caspase3酶的活性。与对照组相比,MK801的使用显着降低了细胞活力,细胞数量,TNL和Caspase3酶的活性。

结论

本研究表明,NMDA治疗在暴露于POX后对海马神经元具有神经保护作用。似乎这些保护作用是由降低caspase3的活性介导的。另外,用MK801预处理细胞对海马神经元有毒性作用。

更新日期:2020-06-29
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