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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 2020년 16권 4호 p.401 ~ 408
Bahrami Farideh, Bahari Zahra, Abolghasemi Reihaneh, Golmanesh Lida, Meftahi Gholam Hossein,
소속 상세정보
 ( Bahrami Farideh ) - Baqiyatallah University of Medical Sciences Neuroscience Research Center
 ( Bahari Zahra ) - Baqiyatallah University of Medical Sciences Faculty of Medicine Department of Physiology and Medical Physics
 ( Abolghasemi Reihaneh ) - Baqiyatallah University of Medical Sciences Faculty of Medicine Department of Community Medicine
 ( Golmanesh Lida ) - Baqiyatallah University of Medical Sciences Neuroscience Research Center
 ( Meftahi Gholam Hossein ) - Baqiyatallah University of Medical Sciences Neuroscience Research Center

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.

키워드

Hippocampal neurons; Paraoxon; NMDA; MK801; Neuroprotection; Neuroprotection

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