Figure 5.
TOMA immunization increases mushroom spines in Tg2576. A, Representative image of dendrite segment displaying spine morphology from 14-month-old Tg2576 mice immunized with a control antibody (IgG group) and TOMA, stained using the Golgi method. Scale bar, 2 μm. B, Quantitative analysis of spine density at <15 μm or >15 μm of plaque edge did not exhibit a difference between treatment groups (two-way ANOVA, Bonferroni's post hoc test). C, Analysis of spine morphology indicates that mice immunized with TOMA increased mushroom-shaped spines compared with the IgG group (*p > 0.05, **p > 0.01, two-way ANOVA, Bonferroni's post hoc test). D, Western blot analysis of the PBS-soluble fraction from brain homogenates of mice immunized with control antibody (IgG group) or TOMA probed with Tau 5, Fyn, GSK3β, and actin antibodies. E, Mice treated with TOMA showed an evident reduction of tau aggregates reactive to Tau 5 (∼64–150 kDa; black bar; **p > 0.008). F, No difference between treatments groups was observed on Fyn immunoreaction. G, Mice immunized with TOMA exhibit a reduction of GSK3β (Y279/Y216) compared with the IgG group (black bar; *p > 0.016). The actin is shown at the bottom. Data reported as OD value ± SEM; two-tailed Student's t test. H, Schematic representation of the possible effects of TOMA in dendritic spines of Tg2576 mice brain. 1, TOMA recognize tau oligomers. 2, TOMA traps tau oligomers linked to Aβ*56. 3, Aβ*56 is disassembled into trimers. 4, Trimeric Aβ aggregate into amyloid plaques, increasing the plaque load in mice brain.