EFFECTS OF NMDA RECEPTORS IN SYNAPSE AND EXTRASYNAPSE OF RAT HIPPOCAMPAL NEURONS ON THE EXPRESSION OF POSTSYNAPTIC DENSITY-95 INDUCED BY AMYLOID-BETA / 解剖学报

ABSTRACT

Objective To investigate the mechanism of the soluble A? oligomers-induced alteration of synaptic proteins. Methods This study applied immunocytochemistry technique to investigate the changes of the expression of postsynaptic density-95(PSD-95) in primary hippocampal neurons, which was exposed to A?_ 25-35 after NMDAR antagonist or agonist treatment. Results The results showed that A?_ 25-35 downregulated PSD-95 protein in a dose- and time-dependent manner. Treatment of cells with MK801 (a general NMDA receptor antagonist) prevented A?-induced PSD-95 degradation. Moreover, when extrasynaptic NMDA receptors were blocked by ifenprodil (a NR2B subunit specific antagonist), the A?-induced downregulation of PSD-95 was significantly attenuated. Whereas, when synaptic NMDA receptors were blocked by bicuculline (a GABA receptor antagonist) in combination with MK801, the PSD-95 degradation did not change significantly.Conclusion The results suggest that A?-induced downregulation of PSD-95 depends on NMDAR activity, and extrasynaptic NMDA receptors may be involved in A?-induced synaptic protein degradation.