The neuroprotective effects of stimulation of NMDA receptors against POX-induced neurotoxicity in hippocampal cultured n
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ORIGINAL ARTICLE
The neuroprotective effects of stimulation of NMDA receptors against POX‑induced neurotoxicity in hippocampal cultured neurons; a morphometric study Farideh Bahrami1,2 · Zahra Bahari2 · Reihaneh Abolghasemi3 · Lida Golmanesh1 · Gholam Hossein Meftahi1 Received: 11 March 2020 / Accepted: 17 June 2020 © The Korean Society of Toxicogenomics and Toxicoproteomics 2020 2020
Abstract 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. Keywords Hippocampal neurons · Paraoxon · NMDA · MK801 · Neuroprotection · Caspase-3 enzyme
Introduction Paraoxon (POX) is an organophosphorus (OP) compound, which widely uses as pesticides and unfortunately, its application during warfare makes it a destructive weapon * Farideh Bahrami [email protected]; [email protected] 1
Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
2
Department of Physiology and Medical Physics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran
3
Department of Community Medicine, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran
worldwide (Yousefpour et al. 2006). POX is a bioactive conformation of the organophosphate pesticide; parathion (Ojha and Srivastava 2014). The POX can inhibit acetylcholinesterase (AChE)
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