NMDA ANTAGONIST BLOCKADE OF AT8-TAU IMMUNOREACTIVE CHANGES IN NEURONAL CULTURES

Antagonists at four distinct regulatory sites on the N-methyl-D-aspart ate (NMDA) receptor were tested for their ability to attenuate NMDA-me diated chronic excitotoxicity and the consequences on AT8 tau immunore activity in neuronal cultures. Excitotoxicity was monitored in culture s by diacetate fluorescein staining. Immunoreactivity of tau phosphory lated at serine 202 was quantified by laser confocal microscopy. The N MDA-receptor antagonists MK801, AP7 and 7-chlorokynurenate significant ly blocked NMDA-induced cell death and significantly reduced AT8 tau i mmunoreactivity. NMDA antagonism by the polyamine site antagonist, ife nprodil, did not completely reverse the increase in AT8 tau immunolabe ling induced by NMDA and did not completely protect NMDA-sensitive neu rons, suggesting an heterogeneity in the NMDA receptor population.