en Neurosciences Neurosciences Original Article Original Article <p><span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:14.0pt"><span style="text-autospace:none"><span style="font-family:Calibri,sans-serif"><span style="font-size:12px;"><span style="font-family:Tahoma;"><span lang="EN-CA">N-Methyl-D-Aspartate (NMDA) receptors are involved in synaptic plasticity and neuronal communication. They have various responses to oxidative stress based on the dosage of agonists or antagonists that may be applied. This study focuses on modulation of NMDA receptors in primary hippocampal neurons in oxidative stress condition to understand the effects of NMDA receptor activation and inhibition. In our experiments, primary hippocampal neurons were treated with NMDA and MK-801 to assess their effect on cell viability and apoptosis. Oxidative stress was induced at different concentrations, to evaluate NMDA receptor activity and the neuroprotective effects of MK-801. Apoptosis rates were specified by applying flow cytometry, and assaying caspase-3 activity. Intracellular calcium levels were monitored using fluorescent dye Fura-2 AM. </span><span lang="EN-ID">NMDA at 200 &mu;M significantly prevented the cytotoxic effect induced by </span><span lang="EN-CA">H₂O₂</span><span lang="EN-ID">(P<0.001). MK-801 with concentrations of 5 to 20 &mu;M, could reverse the cytotoxic effect of </span><span lang="EN-CA">H₂O₂</span><span lang="EN-ID">. As a result, it significantly inhibited the toxicity of </span><span lang="EN-CA">H₂O₂</span><span lang="EN-ID">on neuronal cells (P<0.001), while 40 &mu;M could not reverse its effects.&nbsp; </span><span lang="EN-CA">NMDA (200 &mu;M) increased neuronal survival to 88.3% in the presence of H₂O₂ and prevented apoptosis. MK-801 (5 &mu;M) also elevated cell survival to 87.2%. Treatment with NMDA (200 &micro;M) + H₂O₂also did not show any changes in the Fura-2AM fluorescence compared to the H₂O₂group (P>0.05). However, MK-801+ H₂O₂reduced the effects of H₂O₂on the fluorescence ratio and calcium influx considerably in comparison with the H₂O₂group (P<0.01)</span><span dir="RTL" lang="AR-SA">.</span> Treatment with MK-801 (5 &mu;M) effectively mitigated the effects of <span lang="EN-CA">H₂O₂ on caspase-3 activity compared to the H₂O₂group (P<0.001).</span> </span></span><span lang="EN-CA" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times=""><span style="font-size:12px;"><span style="font-family:Tahoma;">Importantly, the dose-dependent effects of NMDA receptors offer a new path into finding therapeutic strategies for neurodegenerative diseases</span></span><b><i><span style="font-size:12px;"><span style="font-family:Tahoma;">.</span></span> </i></b></span></span><b><i><span lang="EN-ID" style="font-size:10.0pt"><span style="font-family:"Times New Roman",serif"></span></span></i></b></span></span></span></span></span></span></p> NMDA receptors, Oxidative stress, Hippocampal neurons, Neuroprotection, apoptosis 682 693 http://ijmcmed.org/browse.php?a_code=A-10-8203-1&slc_lang=en&sid=1 Marjan Nikbakhtzadeh nikbakhtzadeh@gmail.com 100319475328460034461 100319475328460034461 No Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Asal Behboodian behboudianasal@gmail.com 100319475328460034462 0009-0007-4353-5020 No Department of Pharmacology and Toxicology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran Maryam Mohammadnia maryamf1378@gmail.com 100319475328460034463 0009-0005-0726-6164 No Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Zahra Yaghoobi zyaghoobi89@gmail.com 100319475328460034464 100319475328460034464 No Division of Neurobiology, Faculty of Biology, Ludwig-Maximilians-Universität München, München, Germany Saereh Hosseindoost saereh.hoseindoost@gmail.com 100319475328460034465 100319475328460034465 No Pain Research Center, Neuroscience Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran Afshin Kheradmand kheradmand.a@iums.ac.ir 100319475328460034466 0009-0009-4088-5601 No Iranian National Center for Addiction Studies (INCAS), Tehran University of Medical Sciences, Tehran, Iran Ghorbangol Ashabi gh-ashabi@tums.ac.ir 100319475328460034467 100319475328460034467 Yes Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran