MODULATION OF TAU NEURONAL EXPRESSION INDUCED BY NMDA, NON-NMDA AND METABOTROPIC GLUTAMATE-RECEPTOR AGONISTS

We have analysed changes in tau protein immunoreactivity in rat embryo nic neurons degenerating in response to treatment with N-methyl-D-aspa rtate (NMDA), non-NMDA and metabotropic agonists. Glutamate agonists w ere applied in a Mg++-free and glycine-supplemented medium 8 days afte r initial plating. Cell viability was assessed by fluorescein diacetat e staining and neuronal survival was evaluated by cell counting. Immun ocytochemical and confocal laser microscopic studies used a tau2 monoc lonal antibody. Acute and chronic NMDA treatment induced a concentrati on-dependent increase in intraneuronal tau immunoreactivity. Increased tau immunolabelling during chronic NMDA toxicity was dramatically att enuated by tetrodotoxin and also by 6-cyano-7-nitroquinoxaline-2,3-dio ne. Non-NMDA and metabotropic receptor agonist treatment produced a we aker augmentation in tau2 immunoreactivity. These findings suggest tha t, in this model, glutamate-receptor and sodium-channel coactivation a re together needed to produce changes in tau immunoreactivity.