Figure 10.

Mini-GAGR reduces p-tau and Aβ peptide and improves learning and possibly memory retention in 12-month-old female 3xTg-AD mouse brains. A and B, the cytosols of combined hippocampal and cortical tissues from 3xTg-AD mice treated with either vehicle or 100 nmol of mini-GAGR for 20 days were used for immunoblotting for p-tau and tau. The band densities of tau and p-tau were quantified by ImageJ to obtain average density ± S.E. (error bars) for bar graphs: tau (50 kDa): control versus mini-GAGR (C); p-tau (64 kDa): control versus mini-GAGR (n = 5 animals; **, p < 0.01) (D). E and F, the hippocampal sections of 3xTg-AD mice treated with either vehicle (E) or 100 nm mini-GAGR (F) were stained with anti-Aβ antibody (6E10) and HRP-tagged secondary antibody (scale bar, 250 μm). G, bar graphs show the average number of Aβ-positive hippocampal CA1-CA3 and DG regions of 3xTg-AD mice treated with either vehicle or 100 nm mini-GAGR (n = 6 animals (15 sections)/treatment; **, p < 0.01). G–J, 3xTg-AD mice treated with either vehicle or 100 nm mini-GAGR for 14 days were subjected to the open field paradigm to measure basal locomotor function. There was no difference in vehicle-treated versus mini-GAGR–treated mice regarding mean speed (cm/s) (H) and total distance (cm) (I). J and K, to determine the effect of mini-GAGR on learning and memory in 3xTg-AD mice (n = 7 mice/treatment group), the Barnes maze paradigm was performed. J, primary latency (s) of training days: vehicle-treated mice versus mini-GAGR–treated mice (n = 35 total training trials): training day 1 (p = 0.0309), training day 2 (p = 0.0016), and training day 3 (p = 0.00234). K, primary latency (s) of memory retention: vehicle-treated mice versus mini-GAGR–treated mice: memory retention (p = 0.0587) (*, p < 0.05; **, p < 0.01; ***, p < 0.001; unpaired t test, two-tailed). Data are expressed as mean ± S.E.