Fig. 2: AAV-NF-α1/CPE gene delivery in hippocampus prevents memory loss in 3xTg-AD mice. | Molecular Psychiatry

Fig. 2: AAV-NF-α1/CPE gene delivery in hippocampus prevents memory loss in 3xTg-AD mice.

From: Hippocampal delivery of neurotrophic factor-α1/carboxypeptidase E gene prevents neurodegeneration, amyloidosis, memory loss in Alzheimer’s Disease male mice

Fig. 2

A Experimental design for AAV injection followed by behavioral and pathological analyses of 3xTg-AD mice. 3xTg-AD mice received bilateral hippocampal injections of AAV-GFP or NF-α1/CPE at age 2 months and were evaluated by a series of behavioral tests at age of 7 months. Pathology of the hippocampus of the mice was examined at age ~8 months. B The effect of overexpression of NF-α1/CPE on spatial learning in Morris water maze. 3xTg+GFP mice displayed longer latency compared with nonTg+GFP on day 2, day 3, and day 4, p = 0.0048 for day 2, p = 0.0061 for day 3, p < 0.0001 for day 4, p = 0.0547 for day 5. 3xTg+CPE mice showed no significant difference in latency compared to 3xTg+GFP mice, except on day 4, p = 0.0103 and a trend on day 5. Two-way ANOVA analysis followed by Tukey’s post-hoc multiple comparison test, for factor day [F(4,170) = 27.86, p < 0.0001]. For factor genotype [F(2,170) = 21.11, p < 0.0001]. Day × Genotype: [F(8,170) = 0.7515, p = 0.6459]. n = 12 for nonTg+GFP, n = 11 for 3xTg+GFP, n = 14 for 3xTg+CPE. Values are mean ± SEM. C Overexpression of NF-α1/CPE prevented memory deficit of 3xTg-AD mice in Morris water maze test. 3xTg+GFP mice spent less time in the target area NE, and more time in non-target areas. Both nonTg+GFP and 3xTg+CPE mice displayed similar pattern of time in non-target quadrants and target quadrant. In NE target quadrant, 3xTg+CPE mice spent more time, similar to nonTg+GFP mice, than 3xTg+GFP mice. *p = 0.0025 for 3xTg+CPE compared with 3xTg+GFP. Two-way ANOVA analysis followed by Tukey’s post-hoc multiple comparison test, for factor quadrant [F(3,136) = 8.691, p < 0.0001]. For factor genotype [F(2,136) = 5.942e−006, p > 0.9999]. Quadrant × Genotype: [F(6,136) = 4.475, p = 0.0004]. n = 12 for nonTg+GFP, n = 11 for 3xTg+GFP, n = 14 for 3xTg+CPE. Values are mean ± SEM. D Effect of overexpression of NF-α1/CPE on cognitive function of 3xTg AD mice in novel object recognition test. ANOVA analysis followed by Tukey’s post-hoc multiple comparison test showed no significant differences across groups, but a trend showing memory improvement in 3xTg-AD mice. n = 10 for nonTg+GFP, n = 8 for 3xTg+GFP, n = 12 for 3xTg+CPE. Values are mean ± SEM.

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