NMDA Reduces Tau Phosphorylation in Rat Hippocampal Slices by Targeting NR2A Receptors, GSK3β, and PKC Activities
Figure 4
NMDA-induced changes in Tau phosphorylation are NR2A receptor-dependent. Phosphorylated Tau levels at Ser199-202 were estimated by Western blotting of cell extracts obtained from hippocampal slices. In basal conditions, slices were exposed to an NMDA concentration (1 μM) which had no effect on Tau phosphorylation. In parallel experiments, NMDA-treated slices were preincubated with the NR2B receptor antagonist RO25-6981 (1 μM), the NR2A receptor antagonist NVP-AAM077 (50 nM), or with a mixture of NR2B and NR2A (RO25-6981; 1 μM and NVP-AAM077; 50 nM) receptor antagonists. Representative Western blots and quantitative data on each condition revealed that NMDA-induced reduction of Tau phosphorylation was exacerbated after blockade of NR2B receptors. On the contrary, Tau becomes hyperphosphorylated after blockade of NR2A receptors with NVP-AAM077 (50 nM). The data, expressed relative to total Tau (i.e., Tau-5) levels, are means ± S.E.M. of 3 measurements per cell extract obtained from 8 different rats. For statistical analysis, one-way ANOVA was followed by Newman-Keuls post hoc test. *, **, drug-treated versus control.
