NMDA antagonist blockade of AT8 tau immunoreactive changes in neuronal cultures.
Antagonists at four distinct regulatory sites on the N-methyl-D-aspartate (NMDA) receptor were tested for their ability to attenuate NMDA-mediated chronic excitotoxicity and the consequences on AT8 tau immunoreactivity in neuronal cultures. Excitotoxicity was monitored in cultures by diacetate fluorescein staining. Immunoreactivity of tau phosphorylated at serine 202 was quantified by laser confocal microscopy. The NMDA-receptor antagonists MK801, AP7 and 7-chlorokynurenate significantly blocked NMDA-induced cell death and significantly reduced AT8 tau immunoreactivity. NMDA antagonism by the polyamine site antagonist, ifenprodil, did not completely reverse the increase in AT8 tau immunolabeling induced by NMDA and did not completely protect NMDA-sensitive neurons, suggesting an heterogeneity in the NMDA receptor population.
Couratier
P
P
Unité de Neurobiologie et Pathologie Cellulaire, Laboratoire d'Histologie, Faculté de Médecine, Limoges, France.
Lesort
M
M
Terro
F
F
Dussartre
C
C
Hugon
J
J
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005333:Fetus; D005455:Fluorescent Antibody Technique; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D010880:Piperidines / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000187:drug effects; D016875:tau Proteins / Q000276:immunology*
D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D016875:tau Proteins; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D007736:Kynurenic Acid; C031231:2-amino-7-phosphonoheptanoic acid; C010739:ifenprodil; C057013:7-chlorokynurenic acid