Figure 8.

Compound 11 treatment rescues tau-induced memory impairment. The effects of compound 11 administration on hippocampus-dependent reference memory in the radial arm water maze (RAWM) and contextual fear memory in the contextual fear conditioning (CFC) assay were tested. (A) Human tau oligomer infusion (white triangles) into mice brains creates short-term memory impairment as shown by the significantly greater numbers of errors in the RAWM test compared to control, vehicle-infused mice (black circles) (two-way ANOVA, p < 0.01). Compound 11 administration (light gray diamonds) to the tau-infused animals (5 mg/kg ip, 20 min prior to start of testing) attenuates memory impairment (p < 0.05). Compound 11 administration in control, vehicle-infused mice (dark gray squares), had no effect. (B) Fear conditioning was assessed by exposing mice to a mild shock and then reassessed 24 h later to gauge “freezing” behavior. Tau-infused mice (white bar) experience reduced rates of freezing relative to control mice (“vehicle”; black bar) or control mice administered compound 11 (dark gray bar). Compound 11 administration in tau-infused mice (light gray bar) significantly increases freezing rates, demonstrating protection against tau-related memory impairment (p < 0.05).