Figure 5: Cholesterol facilitates remyelination after cuprizone withdrawal.
From: Dietary cholesterol promotes repair of demyelinated lesions in the adult brain
(a) Scheme depicting the time course of demyelination/remyelination during cuprizone feeding (remyelination after cuprizone withdrawal in purple). The influence of cholesterol on remyelination was assessed by feeding mice cuprizone in normal chow for 4 weeks (4, black bars) followed by ‘induced remyelination’ after cuprizone withdrawal for 1 (4+1) or 2 (4+2) weeks on normal chow or cholesterol supplemented chow. (b) Representative pictures of the corpus callosum of mice after one week (4+1) remyelination. Corresponding quantification is on the right also including values for 2 weeks remyelination (4+2). Assessed were myelination (Gallyas silver impregnation), the number of mature oligodendrocytes (CAII), the number of oligodendrocyte lineage cells (Olig2), activated microglia (MAC3), and astrocytes (GFAP). Each bar represents the mean value from n=4–5 (4 and 4+2) or n=7 (4+1) animals (scale, 100 μm; Two-way ANOVA and Sidak’s post test). (c) Quantification of proliferating OPCs (PCNA positive Olig2 positive) in the corpus callosum of mice after 4+1 treatment paradigm (4+1) or after 12 weeks (12) of cuprizone. Each bar represents the mean of n=6–7 (week 4+1), or n=4 (week 12) animals (Student’s t-test). (d) Quantification of newly differentiated postmitotic oligodendrocytes (TCF4 positive, PCNA negative) in the corpus callosum treated as in c). Each bar represents the mean of n=6–7 (week 4+1), or n=4 (week 12) animals (Student’s t-test). (e) Myelinated axons per 10 μm2 in the corpus callosum at the end of the 4+1 (n=7) and 4+2 (n=4) treatment paradigm (two-way ANOVA and Sidak’s post test). (f) APP positive spheroids per mm2 in the corpus callosum (4+1 n=7; 4+2 n=3–4 animals, two-way ANOVA and Sidak’s post test). (g) Motor learning as assessed by maximum velocity (Vmax) on a complex wheel (n=6 animals), expressed as per cent of the Vmax on a training wheel (mean of the last 7 days before changing to a complex wheel). Statistical evaluation of Vmax was done by Two-way ANOVA (cholesterol effect P<0.0001) and Sidak’s post tests. Asterisks represent significant differences with *P<0.05; **P<0.01; ***P<0.001.
