Fig. 6
In vivo SIRT6 suppression protects from experimentally induced Parkinson-associated pathologies. a Representative movement traces from open field test of WT, BSKO, and BSOX mice treated with MPTP or saline. BSKO mice are more resistant to MPTP-induced motor dysfunction. b Mice are naturally afraid of open spaces and prefer to be next to a wall; the fraction of time the animal explores the center of the arena (red-shaded area in a is inversely related to the animal’s anxiety, which is induced in PD and by MPTP treatment. Quantification of exploratory behavior of SIRT6 transgenic mice treated with MPTP or saline is presented (Mean ± SEM, n ≥ 6, *p < 0.05 by two-tailed t-test. Two-way ANOVA: pgenotype = 6.6•10− 5, pMPTP = 3.8•10− 3, pMPTP x Gen = 4.8•10− 2). c Quantification of motor function of SIRT6 transgenic mice treated with MPTP or saline is presented via bar graphs (average distance covered per minute, mean ± SEM). BSKO animals are protected from PD-associated mobility decline (n ≥ 6, *p < 0.05 by two-tailed t-test. Two-way ANOVA: pgenotype = 4.8•10− 8, pMPTP = 8.9•10− 3, pMPTP x Gen = 0.675). d Representative immuno-histochemical analysis of substantia nigra pars compacta of WT, BSKO, and BSOX mice treated with MPTP or saline. 15 μM sections were stained with anti-Tyrosine Hydroxylase to visualize dopaminergic neurons (brown stain) and counterstained with hematoxylin (purple stain). BSKO animals demonstrate reduced reduction of DA neurons after MPTP treatment, and BSOX animals have exaggerated neuronal death. e Quantification of histochemical analysis presented on d. Boxplots illustrate mean values and standard deviation of the relative abundance of DA neurons; box whiskers represent 5th and 95th percentiles of data distribution. Each circle is a separate animal. Black boxes – WT, yellow – BSKOs, and blue – BSOX animals (n ≥ 6, **p < 0.01, and ***p < 0.001 by two-tailed t-test, two-way ANOVA: pgenotype = 6.2•10− 2, pMPTP = 8.2•10− 11, pMPTP x Gen = 4.4•10− 3). f Representative immuno-histochemical analysis of striatum of WT, BSKO, and BSOX mice treated with MPTP or saline. DA neuron projections are visualized with anti-TH antibody. Drop in the density of dopaminergic projections after MPTP injections is mitigated in BSKO animals, and is exaggerated in BSOX mice. g Quantification of histochemical analysis, such as those presented on (f). Boxplots illustrate the mean density of dopaminergic projections in striatum of experimental animals; the box structure and coloring is the same as in e, (n ≥ 6, *p < 0.05, and ****p < 0.0001 by two-tailed t-test, two-way ANOVA: pgenotype = 2.3•10− 6, pMPTP = 3.5•10− 16, pMPTP x Gen = 1.1•10− 5)