A Research on the Role and Mechanism of N-Methyl-D-Aspartate Receptors in the Effects of Silver Nanoparticles on the Electrical Excitability of Hippocampal Neuronal Networks

The purpose of this paper is to explore the role and mechanism of N-Methyl-D-Aspartate (NMDA) receptors in the effects of silver nanoparticles (SNPs) on the electrical excitability of hippocampal neuronal networks. First, the cytotoxicity of different concentrations of SNPs was evaluated and screened by MTT experiment, then the Voltage Threshold Measurement Method (VTMM) was employed to study the effects of SNPs on the electrical excitability of hippocampal neuronal networks under non-cytotoxic (5 μM) and cytotoxic (100 μM) concentrations after different action times. The role of NMDA receptors in the effects of SNPs on the electrical excitability of hippocampal neuronal networks was investigated through the NMDA receptor antagonist MK-801. Then, the effects of SNPs on the number of NMDA receptors and the Ca2+ content in hippocampal neurons were further investigated, and the relationship between these changes and neuronal networks electrical excitability was discussed. The results of voltage threshold (VTh) test showed that non-cytotoxic 5 μM SNPs has an excitatory effect on hippocampal neuronal networks, while the effect of cytotoxic 100 μM SNPs gradually changed from excitatory to inhibitory with the extension of action time. It was found that SNPs could increase the electrical excitability of neuronal networks by activating NMDA receptors through the experiments with MK-801 antagonists. Moreover, the fluorescent staining experiments showed that the activation of NMDA receptors by SNPs can lead to an increase in the intracellular Ca2+ content, and then trigger a negative feedback regulation mechanism of neurons between the number of NMDA receptors and intracellular Ca2+ content. The high Ca2+ content in neurons can also decrease neurons’ cell viability, which in turn leads to changes in the electrical excitability of the neuronal networks.