Blockade of Lysosomal Acid Ceramidase Induces GluN2B-Dependent Tau Phosphorylation in Rat Hippocampal Slices
Figure 4
Tau hyperphosphorylation is mediated by calcium and is dependent on GluN2B receptor activation. Phosphorylated Tau levels at Ser262 were estimated by Western blotting of cell extracts obtained from hippocampal slices. In basal conditions, slices were only exposed to the acid ceramidase inhibitor d-NMAPPD (25 μM, 3 h). In parallel experiments, d-NMAPPD-treated slices were preincubated (a) with the nonpermeable calcium chelator BAPTA (10 μM) or with the global NMDA receptor antagonist AP-5 (50 μM) and (b) with the GluN2B receptor antagonist RO25-6981 (1 μM) or the GluN2A receptor antagonist NVP-AAM077 (50 nM). Summary data are expressed relative to total Tau (Tau-5) levels and shown in the bar graph (means ± SEM of 6 different experiments). For statistical analysis, one-way ANOVA was followed by Newman-Keul’s post hoc test. , drug treated versus controls.
