Fig. 6: T cell-driven axonal spheroid formation is initiated in proximity to constricted paranodal domains. | Nature Communications

Fig. 6: T cell-driven axonal spheroid formation is initiated in proximity to constricted paranodal domains.

From: Microglia-mediated demyelination protects against CD8+ T cell-driven axon degeneration in mice carrying PLP defects

Fig. 6: T cell-driven axonal spheroid formation is initiated in proximity to constricted paranodal domains.

a Representative electron micrographs of optic nerve longitudinal sections from 3- to 9-month-old Wt (top), PLPmut (middle), and PLPtg mice displaying putative subsequent stages of axonal spheroid formation. Progressive constriction of axon diameters by oligodendrocytic paranodal loops (light red pseudocolor) correlates with the accumulation of disintegrating mitochondria (exemplarily shown in light blue pseudocolor), juxtaparanodal swelling, and fragmentation in PLPmut mice. Early-stage axonal spheroids in PLPtg mice are often associated with myelin-phagocytosing microglia (green pseudocolor). Scale bar, 0.5 μm. b Fibers with constricted paranodal domains are also detectable in cross-sections of optic nerves from PLPmut mice. Scale bar, 0.5 µm c Electron microscopy-based quantification of minimum paranodal axon diameters in 9-month-old Wt, PLPmut, and PLPtg mice (each circle represents the value of one paranodal region and each diamond represents the mean value of one mouse), colours indicate stages of spheroid formation, n = 5 mice and 25 paranodes per group, one-way ANOVA with Tukey’s multiple comparisons tests, F (2, 12) = 17.5, P < 0.001. d Analysis of the form factor of paranodal loops reveals decreased circularity along with progressive stages of spheroid formation (each circle represents the mean value of one paranodal region, n = 5 mice and 56 paranodes: 24 normal, 19 stage 1, 13 stage 2, one-way ANOVA with Tukey’s multiple comparisons test, F (2, 53) = 30.54, P < 0.001). e Electron microscopy-based quantification of minimum paranodal axon diameters in 9-month-old Wt, PLPmut (as shown in panel c), and PLPmut/Rag1−/− mice (n = 5 mice and 25 paranodes per group, one-way ANOVA with Tukey’s multiple comparisons test, F (2, 12) = 15.55, P < 0.001). f Quantification of small (S) and large (L) SMI32+ axonal spheroids in 3- and 9-month-old Wt, PLPmut, and PLPmut/Rag1−/− mice (each circle represents the mean value of one mouse, n = 5 mice per group, two-way ANOVA with Tukey’s multiple comparisons test, F (5, 48) = 36.19, P < 0.001). g Electron microscopy-based estimation of total axonal numbers in the optic nerves. Axon loss is significantly milder in PLPmut/Rag1−/− than PLPmut mice (n = 5 mice per group, two-way ANOVA with Tukey’s multiple comparisons test, F (2, 24) = 44.33, P < 0.001). Data are presented as the mean ± s.d.

Back to article page