Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer's Disease
Cortical neuronal cultures were treated with (A) S8 and vehicle (Veh) or (B) TC-2153 and vehicle (0.05, 0.1, 1, and 10 µM) for 1 h. Phosphorylation of GluN2B (Y1472), Pyk2 (Y402), and ERK1/2 (Y204/187) were significantly higher after treatment of cultures with S8 (A) or TC-2153 (B) (*p<0.05, **p<0.01, ***p<0.001, one-way ANOVA with post hoc Bonferroni test). Data represent the phospho-signal normalized to total protein and then to GAPDH (mean ± s.e.m., n = 4). C57BL/6 mice (3–6 mo) were injected with (C) S8 (0.5, 1, 3 mg/kg, i.p.) or (D) TC-2153 (i.p., 1, 3, 6, 10 mg/kg, i.p.) and were sacrificed 3 h later. Cortices were microdissected and lysates spun down to P2 fraction and prepared for Western blotting. Tyrosine phosphorylation status was probed with phospho-specific antibodies to pGluN2B: Tyr1472, pPyk2: Tyr402, and pERK1/2: Tyr204/187 (*p<0.05; **p<0.01; one-way ANOVA with post hoc Bonferroni test). Data represent the phospho-signal normalized to the total protein signal and then to GAPDH (mean ± s.e.m., n = 3).