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California 0% Overexpression of SIRT1 in hippocampus does not alter LTP or associative memory. A , Western blot shows ∼16-fold SIRT1 protein increase in hippocampus of NeSTO mice compared with control Nestin–Cre animals. The numbers below show SIRT1 levels relative to actin. B , I/O curve of field EPSP slope versus current input (microamperes) is shifted to the left in NeSTO mice (n = 14; gray circles) compared with Nestin–Cre (n = 10; black circles; p < 0.0001, two-way ANOVA), suggesting increased basal synaptic excitability. C , Paired-pulse facilitation reveals normal presynaptic events in NeSTO mice (n = 5 each genotype). D , Similar LTP was elicited by 5 × 3 and 10 × 10 TBS (EPSP slopes; n = 7 each genotype) in mice overexpressing wild-type or increased levels of SIRT1. E, F , Fear conditioning to context ( E ) or tone ( F ) in Nestin–Cre (n = 14) and NeSTO animals (n = 18) show similar associative learning capacities in both strains. Data represent means ± SEM.
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SIRT1-KO mice show spatial learning and memory impairment. A , Success of SIRT1-KO mice (n = 5; open circles) to find the escape box in the Barnes maze was lower than for WT mice (n = 6; *p < 0.001; filled circles). B , Latency to find the escape box significantly decreased in WT mice compared with SIRT1-KO (*p < 0.001). C, D , Number of total errors ( C ) and deviations from the first error ( D ) (*p < 0.001) were both higher in SIRT1-KO mice than WT mice. E, F , Search strategy of WT ( E ) and SIRT1-KO ( F ) mice (serial strategy, yellow; spatial strategy, green; random strategy, red). Data represent means ± SEM. Statistical significance values correspond to the differences between curves analyzed all over the acquisition phase. *p < 0.05, days with statistical significance.
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