Figure 8.

PS19 Tg mice have increased p-tau and evidence of hippocampal degeneration. A, Representative photomicrographs (5×) of the hippocampus in nTg and Tg mice treated with vehicle or ISRIB. Sections stained using DAPI, fluoro-Nissl, and antibody directed at p-tau (AT8). Boxes indicate the ROIs. B, Representative photomicrographs (40×) of the endal limb of the DG in nTg and Tg mice treated with vehicle or ISRIB. Sections stained using DAPI, fluoro-Nissl, and antibody directed at p-tau (AT8). C, Quantification of AT8 in the DG. Tg mice treated with ISRIB have an increased number of p-tau-immunoreactive inclusions in the DG compared to nTg mice treated with vehicle. Error bars indicate SEM; *p < 0.05. D, Quantification of AT8 in the hippocampus. Tg mice have an increased number of p-tau-immunoreactive inclusions throughout CA1, CA3, and the DG compared to nTg mice treated with vehicle. Error bars indicate SEM; **p < 0.01. E, Representative photomicrographs (2.5×) of brain sections from nTg and Tg mice treated with vehicle or ISRIB. Arrows indicate the pyramidal cell layer of CA1. Sections stained using fluoro-Nissl. F, Quantification of CA1 layer thickness. Tg mice have significant reductions in CA1 compared to nTg mice treated with vehicle. nTg vehicle, n = 7; nTg ISRIB, n = 7; Tg vehicle, n = 7; Tg ISRIB, n = 7. Error bars indicate SD; **p < 0.01.