Fig. 8

SIRT6 regulated remyelination and functional recovery via CHI3L1 in LPC induced demyelination A Schematics of treatment strategies. Transfection of astrocytes with AAV9 inducing astrocyte-specific GFaABC1D promoter-driven SIRT6 overexpression or CHI3L1 overexpression, with stereotaxical injection into CC, 5 days prior to exposure to LPC injuries in 8-week-old C57BL/6 mice. Behavioral tests were conducted between 14 ~ 28 dpi. Tissues were collected for histopathological, biochemical analyses at 14 dpi. B-D The MWM test was conducted. The escape latency at training days 1–5 (B) (Two-way ANOVA). In the probe test, the time spent in target quadrant (C) and the number of platform crossings (D) were compared among groups (one-way ANOVA with Tukey’s multiple-comparison test, n = 6 per group). E Rotarod test (one-way ANOVA with Tukey’s multiple-comparison test, n = 6 per group). F Representative swim trajectories of each group in orientation navigation trials and spatial exploration trials. G Representative images of LFB staining (blue) in demyelinated lesions in Control and LPC mice treated by PBS, AAV-SIRT6OE or AAV-SIRT6OE + AAV-CHI3L1OE, scale bar = 100 μm. H Statistical analysis for demyelinated areas (one-way ANOVA with Tukey’s multiple-comparison test, n = 5 per group). I ChIP-qPCR analysis to determine the histone acetylation of CHI3L1 promoter in AAV infected CC (two-tailed unpaired Student’s t-test, n = 3 per group). Data: P < 0.05 is statistically significant. All values are denoted as the mean ± SD