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. Author manuscript; available in PMC: 2016 Apr 1.
Published in final edited form as: Nat Med. 2015 Sep 21;21(10):1154–1162. doi: 10.1038/nm.3951

Figure 5. Salsalate Treatment Prevents Hippocampi Atrophy, Reduces Tau Pathology and Rescues Spatial Memory Deficits in PS19 Mice.

Figure 5

(a–b) SSA treatment prevented hippocampal volume loss. (a) Representative nissl staining of hippocampus from 8-month-old NTG and PS19 mice before the treatment (non-treated, NT), 10 month-old vehicle-treated NTG, vehicle- or SSA-treated PS19 mice. Scale bar, 500 μm. (b) Quantification of hippocampal volume. n=6 (NTG, NT), 9 (PS19, NT), 8 months old. n=9 (female NTG, veh), 6 (female PS19, veh), 6 (female PS19, SSA), 10–11 months old, ** p < 0.01, one-way ANOVA, Tukey-Kramer post hoc analyses. (c–d) SSA treatment reduced NFTs in PS19 mice. (c) Example of Gallyas staining images of vehicle-treated female NTG mice, and female PS19 mice treated with vehicle or SSA. Scale bar: 250 μm (upper); 25 μm (middle, lower) (d) Quantification of silver-positive cells or neurites in neocortex and hippocampus (CA1+CA3) of vehicle- or SSA treated PS19 mice. n=8 mice/genotype/treatment, 10–11 months old, * p < 0.05, unpaired student t-test. (e–h) SSA treatment ameliorated spatial memory loss in fixed-location dry maze and in MWM. (e) No significant difference in learning rate was observed among the groups in fixed location dry maze; Day 1–2, training with visible hole; Day 3–5, learning with hidden hole. (f) NTG or SSA-treated PS19 mice, but not vehicle-treated PS19 mice, showed preference to the target quadrant. n=10 (female NTG, veh), 8 (female PS19, veh), 8 (female PS19, SSA), 10–11 months old. (g) Learning rate did not differ among the groups in MWM. (h) SSA treatment restored spatial memory deficits in PS19 mice. NTG or SSA-treated PS19 mice, but not vehicle-treated PS19 mice, showed preference to the target quadrant. n=13 (male NTG, veh), 15 (male NTG, SSA), 11 (male PS19, veh), 10 (male PS19, SSA), 9–10 months old. The multilevel mixed-effects linear regression model was used to assess the learning curve (e, g). *** p < 0.001, ** p <0.01, * p <0.05, paired student t-test. Values are means ± SEM (b, d, e–h). NTG, non-transgenic.