CA1 Nampt knockdown recapitulates hippocampal cognitive phenotypes in old mice which nicotinamide mononucleotide improves

Old mice show significant decreases in hippocampal NAD+ levels but retain their spatial acquisition and learning capabilities. a Hippocampal NAD+ levels in male mice at 2, 7, and 19 months of age (n？=？6; *p？<？0.05, one-way ANOVA with LSD post hoc test). b Total ambulations were measured in the 1？h locomotor activity tests on PBS-treated 2-month-old (n？=？12), PBS-treated 20-month-old (n？=？14), and NMN-treated 20-month-old (n？=？14) male mice. c–h Evaluation of PBS-treated 2-month-old (n？=？12), PBS-treated 20-month-old (n？=？14), and NMN-treated 20-month-old (n？=？14) male mice in the MWM tests. Escape path lengths and swimming speeds during the cued (c, d) and place (e, f) conditions are shown. Platform crossings (g) and times spent in each quadrant (h) during the probe condition are also shown. Data are presented as mean？±？SE. Statistical analyses were conducted by two-way repeated measures ANOVA for (b–f) and one-way ANOVA for (a, g, h). Significant group effects and group by time or sessions interactions are denoted by symbols at the right sides of the graphs (§ and ？, respectively). b–f *p？<？0.05, **, ##, $$p？<？0.01, ***, ###p？<？0.001 (*, **, *** for PBS-treated young vs. PBS-treated old mice; #, ## for PBS-treated young vs. NMN-treated old mice; $$ for PBS-treated old vs. NMN-treated old mice). g *p？<？0.05 for the comparison to PBS-treated young mice. h Significant spatial bias toward the target quadrant is denoted (*