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. Author manuscript; available in PMC: 2018 Apr 16.
Published in final edited form as: Nat Med. 2017 Oct 16;23(11):1377–1383. doi: 10.1038/nm.4413

Figure 3. Both blockade of ΔFosB signaling and direct rescue of calbindin expression ameliorate spatial memory deficits in APP mice.

Figure 3

(a) Object location test performance of NTG and APP mice treated with bilateral hippocampal infusion of AAV carrying either ΔJunD/eGFP (AAV-ΔJunD) or eGFP alone (AAV-eGFP) (paired t-tests: AAV-eGFP/NTG, n=8 mice, t7=2.9, *p=0.023; AAV-eGFP/APP, n=9 mice, t8=0.55, p=0.6; AAV-ΔJunD/NTG, n=7 mice, t6=3.63, **p=0.01; AAV-ΔJunD/APP, n=9 mice, t8=5.84, ***p=3.86×10-4). (b) Histone 4 lysine acetylation on the Calb1 promoter of NTG and APP mice treated with AAV-eGFP or AAV-ΔJunD (n=6 mice/group; two-way ANOVA: genotype F1,20=3.07 p=0.095, treatment F1,20=2.98 p=0.1, interaction F1,20=7.73 p=0.012; Tukey's HSD: AAV-eGFP/NTG vs. APP *p=0.021, AAV-ΔJunD/NTG vs. APP p=0.89). (c,d) Quantification and representative images of calbindin IR in NTG and APP mice treated with AAV-eGFP or AAV-ΔJunD (n=6 mice/group except AAV-eGFP/APP n=5 mice; two-way ANOVA: genotype F1,19=13.82 p=0.0015, treatment F1,19=0.58 p=0.46, interaction F1,19=3.45 p=0.079; Tukey's HSD: AAV-eGFP/NTG vs. APP **p=0.0056, AAV-ΔJunD/NTG vs. APP p=0.44). In panel (d), corresponding images of ΔFosB IR (middle row) and JunD/ΔJunD IR (bottom row) are also shown. Scale bar = 50 μm. (e,f) Quantification and images of calbindin IR in APP mice treated with either AAV carrying either CMV promoter-driven calbindin/eGFP (AAV-Calb1) or AAV-eGFP (n=8 mice/group; Student's t-test: t14=3.36, **p=0.0046). In panel (f), corresponding images of ΔFosB IR (right) are also shown. Scale bar = 50 μm. (g) Object location test performance of APP mice treated with AAV-eGFP or AAV-Calb1 (n=8 mice/group; paired t-tests: AAV-eGFP, t7=-0.45, p=0.67; AAV-Calb1, t7=3.89, **p=0.0059). Error bars represent SEM.