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. Author manuscript; available in PMC: 2023 Oct 1.
Published in final edited form as: Nat Neurosci. 2023 Mar 16;26(4):555–569. doi: 10.1038/s41593-023-01271-1

Fig. 8 ∣. Failed myelin repair after oligodendrocyte 2Phatal in aging.

Fig. 8 ∣

(a) Time-series of an aged oligodendrocyte (arrow) degenerating following 2Phatal. (b) Survival curves of oligodendrocytes after 2Phatal in young (n=36 cells, 4 mice) and aged mice (n=14 cells, 3 mice) (log rank (mantel cox) test, error bars are SEM). The average time to oligodendrocyte death after 2Phatal in young and aged mice (two-tailed, unpaired t-test, error bars are SEM). (c) Changes in myelin (orange arrowheads) and oligodendrogenesis (green arrows) in the territory of an oligodendrocyte targeted with 2Phatal (orange arrows), in a young (top) and aged mouse (bottom). (d) The change in myelin sheath density between day 0 and day 60 in the territory surrounding an oligodendrocyte targeted with 2Phatal, in young (n=10 cells, 4 mice,) and aged mice (n=10 cells, 3 mice, two-way ANOVA with Sidak correction for multiple comparisons). The change in sheath density in young mice and aged mice (young n=10 cells, 4 mice, aged n=10 cells, 3 mice, two-tailed, unpaired t-test, error bars are SEM, p = 0.000006). (e) Time-series showing the degeneration of a myelin sheath (orange arrow) over weeks in an aged animal with oligodendrocytes targeted with 2Phatal. (f) The percentage of sheaths exhibiting thinning, retraction, balloons, or swellings over 60 days after 2Phatal (n=239 sheaths, 3 mice). (g) Total prevalence of each observed myelin pathology in 2Phatal mice (n=239 sheaths, 3 mice) that had the specific pathology for least one time point over 60 days of imaging. Myelin balloon formation is subdivided into the eventual fate of observed balloons including, balloons that were stable through the cessation of imaging (gray; n=3), balloons that resulted in sheath degeneration (red; n=5), and balloons which formed and then were subsequently repaired (green; n=110). (h) Total breakdown of all sheaths without any observed pathology (gray), with pathology (blue), sheaths that degenerate (red), and sheaths that were remyelinated (green, *we did not observe any remyelination of sheaths analyzed) in aged mice that were targeted with 2Phatal (n=239 sheaths, 3 mice). (i) Myelin sheath fate diagram demonstrating the progression of pathology of a subset of sheaths.