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. 2019 Oct 30;142(12):3806–3833. doi: 10.1093/brain/awz319

Figure 7.

Figure 7

Nanocarrier delivery of a Wnt/β-catenin pathway activator L803mts in microglia reduces IL-1β-induced hypomyelination and memory deficit. (A) Representative images of in vivo uptake of 3DNA by IBA1+ cells in subventricular white matter at P5 after intraperitoneal injections of 3DNA L803mts Cy3 or 3DNA SCR Cy3 (500 ng/injection). Scale bar = 40 μm. (B) Min to max box and whiskers plot of Mbp mRNA by qRT-PCR in the anterior brain of mice at P10. mRNA levels are presented as a fold-change relative to the 3DNA SCR Cy3/PBS group (one way-ANOVA with Newman-Keuls’s test, *P < 0.05, **P < 0.01, n = 9–12/group). See also Supplementary Fig. 5C and D. (C) Representative image of actin and MBP immuno-blot; and (D) the min to max box and whiskers plots of quantification of the four isoforms of MBP in the anterior brain of mice at P15. Protein levels were normalized to actin and are presented as a fold-change relative to the 3DNA SCR Cy3/PBS group (one way-ANOVA with Newman-Keuls’s test, *P < 0.05, **P < 0.01, ***P < 0.001, n = 6–8/group). (E) Representative image of electron microscope (EM) image of the corpus callosum from mice at P30. (F) Violin plots of the G-ratios from the EM analysis showing improvements in the Wnt agonist group, 3DNA L803mts (Kruskall-Wallis test, ***P < 0001 n = 4–5/group). Microglial targeted Wnt agonism also induced functional improvements. (G) Data from trials of the Barnes maze for spatial learning. (H) Short-term memory retention and (I) long-term memory retention in 3-month-old mice. See also Supplementary Fig. 6. Memory retention present in the 30-s trial period on Day 5 of the test (probe trial, in H) was measured by recording of the distance travelled in the target sextant (min to max box and whiskers plot, univariate t-test *P < 0.05 n = 10/group). (I) The long-term memory deficits were measured via the distance travelled to reach the target on the 15th day after the start of testing (min to max box and whiskers plot, one-way ANOVA with Bonferroni post hoc was used **P < 0.01. n = 9/group).