Figure 3.

Fingolimod and Teriflunomide Attenuate the Elevation of Sn⁺ Microglia/Macrophage Numbers in CLN1 and CLN3 Disease Models

(A) Representative immune fluorescence microscopy of Sn⁺ microglia/macrophages in longitudinal optic nerve sections from 6-month-old Ppt1^+/+, Ppt1^−/−, fingolimod-treated Ppt1^−/− (+ FTY720), and teriflunomide-treated Ppt1^−/− (+ Teriflunomide) mice (top) and 17-month-old Cln3^+/+, Cln3^−/−, fingolimod-treated Cln3^−/− (+ FTY720), and teriflunomide-treated Cln3^−/− (+ Teriflunomide) mice (bottom). Scale bar, 20 μm. (B) Quantification of Sn⁺ microglia/macrophages (percentage of CD11b⁺) in optic nerve sections. The numbers of Sn⁺ cells were significantly increased in the CLN1 and CLN3 disease models compared with WT mice. This increase was attenuated in both models by treatment with fingolimod as well as teriflunomide for 150 days (n = 5 mice/group). One-way ANOVA and Tukey’s post hoc tests. *p < 0.05, **p < 0.01, ***p < 0.001. (C) Representative light microscopy of Sn⁺ microglia/macrophages in coronal sections of S1BF cortex from 6-month-old Ppt1^+/+, Ppt1^−/−, fingolimod-treated Ppt1^−/− (+ FTY720), and teriflunomide-treated Ppt1^−/− (+ Teriflunomide) mice (top) and 17-month-old Cln3^+/+, Cln3^−/−, fingolimod-treated Cln3^−/− (+ FTY720) and teriflunomide-treated Cln3^−/− (+ Teriflunomide) mice (bottom). Note the reduction of cortical atrophy in treated Ppt1^−/− mice. Scale bar, 50 μm. (D) Higher magnification of Sn⁺ microglia/macrophages. Scale bar, 20 μm.