Figure 6.
Lentiviral PGRN overexpression prevents neuronal loss and hippocampus-dependent memory deficits in 5xFAD mice. (a,b) Effects of PGRN overexpression on neuronal loss. (a) Representative images of NeuN staining in hippocampus. Scale bar, 200 μm. Bottom panels are higher magnification images of top panels. (b) Quantification of number and area of NeuN+ cells in the hippocampus. n = 12, n = 14, n = 14 from 6 (NI), 7 (Lenti-Ctrl), or 7 (Lenti-PGRN) mice, *, P < 0.05, **, P < 0.01, mixed effects model and multiple comparison correction using the method of Holm. (c,d) Cued Y-maze spatial memory performance in PGRN-overexpressing 5xFAD (c) or non-transgenic (d) mice. n = 9, n = 12, n = 13, *, P < 0.05; NS, not significant, paired student’s t-test (c). Lenti-Ctrl-injected 5xFAD mice were analyzed by Wilcoxon signed rank test of pairs. n = 6, n = 7, **, P < 0.01, paired student’s t-test (d). (e–h) Contextual fear conditioning in 5xFAD (e,f) or non-transgenic (g,h) mice. (e,g) Quantification of freezing time on Day 1 for 3 min pre-shock (baseline) and on Day 2 for 1 min post-shock. n = 7, n = 12, n = 13 (e); n = 6, n = 7 (g). (f,h) Quantification of freezing time in 3-min intervals on Day 5 testing. n = 7, n = 12, n = 13, *, P < 0.05, by analysis of min 6–12 by mixed effects model and Tukey-Kramer post-hoc analysis (f). Two mice from the NTG/NI group were statistical outliers (> 2 S.D.) due to low freezing during testing, thus excluded from analysis. n = 6, n = 7, not significant (NS) by analysis of min 6–12 by mixed effects model and Tukey-Kramer post-hoc analysis (h).