1. SIRT1 deletion exacerbates premature lethality and synapse loss in tauP301S mice.
SIRT1 deletion exacerbates premature lethality and synapse loss in tauP301S mice. A, Kaplan–Meier survival analysis showed a significant reduction of survival rate in tauP301S mice with SIRT1 deletion than tauP301S mice without SIRT1 deletion. P301S−;Cre−, n = 19; P301S−;Cre+, n = 18; P301S+;Cre−, n = 18; P301S+;Cre+, n = 20. Log-rank (Mantel–Cox test), *p = (P301S+;Cre− vs P301S+;Cre+). B, C, Synapse loss was exacerbated in tauP301S mice with SIRT1 deletion. B, Synaptophysin (SY38) immunostaining in both the frontal cortex (FC) and hippocampus (HP). Scale bars: first row, 250 μm; second and third rows, 25 μm. C, Quantification of percentage of SY38-positive area showed a significant reduction of synapses in tauP301S mice with SIRT1 deletion. n = 6 mice per genotype, **p < 0.01, one-way ANOVA, Tukey's post hoc test. D, Formation of neurofibrillary tangle (NFT) was not altered in tauP301S mice with SIRT1 deletion. Gallyas silver staining was performed to investigate the degree of NFT in either tauP301S mice or tauP301S mice with SIRT1 deletion. No NFT was identified in tauP301S-negative mice as expected. n = 5–6 mice per genotype. Scale bars: first row, 250 μm; second row, 25 μm. Values are means ± SEM.
Sang-Won Min et al. J. Neurosci. 2018;38:
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