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The lack of SIRT1 does not affect exploratory behavior but leads to deficits in immediate memory. A, B , SIRT1-KO mice showed normal exploratory behavior in the open field compared with WT as revealed by distance traveled ( A ) and time spent in the center of the arena ( B ) (n = 4 per genotype; WT, 3.6 ± 1. 05%; KO, 3.4 ± 1.5%). C , Novel object recognition test shows normal discriminatory ability to a novel object in SIRT1-KO mice (n = 4 per genotype; training WT, 7 ± 5; training KO, 12 ± 6; test WT, 30 ± 12; KO test, 40 ± 13; p > 0.5). D , Decreased spontaneous alternation in the Y maze compared with WT mice (n = 16 per genotype; WT 58 ± 4 vs KO 48 ± 2%; *p < 0.05). Data represent means ± SEM. E , Cross sections of retinas from SIRT1-KO and WT mice show normal morphology of all retinal layers (ONL, outer nuclear layer; INL, inner nuclear layer; GCL, ganglion cell layer) by hematoxylin and eosin staining as well as by isolectin (red), GFAP (green), and DAPI (blue) staining ( F ). Scale bars, 100 μM.
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Video Robot Review - Video-Robot.com 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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