Triclosan-Evoked Neurotoxicity Involves NMDAR Subunits with the Specific Role of GluN2A in Caspase-3-Dependent Apoptosis

摘要: Triclosan (TCS) is an antimicrobial agent that used extensively in personal care and sanitising products. A number of studies have shown the presence TCS different human tissues such as blood, adipose tissue, liver, brain well breast milk urine. N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels widely expressed central nervous system which play key roles excitatory synaptic transmission. There is, however, no data on involvement NMDAR subunits apoptotic neurotoxic effects TCS. Our experiments first to show at environmentally relevant concentrations evoked NMDA-dependent neocortical neurons primary cultures, MK-801, uncompetitive NMDA receptor antagonist, reduced levels TCS-induced ROS production caspase-3 activity LDH release. caused a decrease protein expression all studied (GluN1, GluN2A, GluN2B) were measured 3, 6 24 h post-treatment. However, 48 h experiment, level GluN1 subunit returned control level, other showed tendency increase. In TCS-treated cells, profiles up similar mRNA but not GluN2B mRNA. this study, cells transiently transfected with GluN1, GluN2A or siRNA exhibited release, suggests action According our data, mainly responsible for neuronal cell death evidenced by neutral red uptake, whereas was involved caspase-3-dependent apoptosis. We suggest TCS-evoked apoptosis neurotoxicity could be related transient degradation mouse neurons. Furthermore, recycling response possible. Because transfections specific did completely abolish compared negative NMDAR-independent mechanisms also