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. Author manuscript; available in PMC: 2024 May 20.
Published in final edited form as: Nat Neurosci. 2024 Mar 27;27(5):846–861. doi: 10.1038/s41593-024-01613-7

Figure 5 |. Cuprizone affects gray and white matter oligodendrocyte populations similarly.

Figure 5 |

a) 3P imaging timeline to track cuprizone-induced OL loss and gain. b) Depth of PPC and subcortical WM that was imaged over 66 days. c) Percentage of the corpus callosum that was imaged/ analyzed longitudinally did not differ by group. d) Time series of cuprizone-mediated OL loss in the deep cortex. e) Cumulative OL loss (%) over time in the GM for individual mice. f) Time series of cuprizone-mediated OL loss in the WM. g) Cumulative OL loss (%) over time in the WM for individual mice. h) The number of OLs lost per 350×350×60μm imaging volume was lower in the GM vs. WM (p=0.024). i) OL population loss dynamics are similar across regions. j) No difference in the total % loss for the GM vs. WM. k) No difference in the rate of % loss for the GM vs. WM. l) No difference in the inflection point of the population loss curve. m) The rate of GM and WM population loss, binned by 2–3 week intervals. No differences between the GM and WM at each time point. OL loss increased earlier in the GM vs. WM (p=0.018, Weeks −2–0 vs. −3 GM; p=0.018, Weeks 1–2 vs. −3 GM; p=0.018, Weeks 1–2 vs. −3, WM). n-p) Images of the distribution of MOL1, MOL2/3, and MOL5/6 subpopulations in the PPC and WM at 4-days post-cuprizone. q) Cuprizone reduced expression of all three markers in both regions (Healthy P140 to Cup.+4d; p=0.007, MOL1-GM; p=0.038, MOL1-WM; p=0.004, MOL2/3-GM; p=0.004, MOL2/3-WM; p=0.0001, MOL5/6-GM; p<0.0001, MOL5/6-WM). r) GM vs. WM transcriptional heterogeneity at four days post-cuprizone (MOL1, p=0.011; MOL2/3, p=0.0097; MOL5/6, n.s.). Data in k,l were calculated from the Gompertz curve parameters. Data in a-m represent n=6 mice/group, q-r represent n=5 mice (Cup. +4d) and n=8 mice (Healthy P140), two sections per mouse. *p<0.05, **p<0.01, ***p<0.001, n.s., not significant; for growth curves, cubic splines approximate the measure of center and error bars are 95% confidence intervals, box plots represent the median, interquartile ranges and the minimum/maximum values; Line plots connect the mean at each time point. Statistical tests were unpaired, two-sided Student’s t-tests for equal/unequal variance (h,j,k,q), Steel multiple comparisons with control (m) or two-sided Wilcoxon rank sum (l,q,r). For detailed statistics, see Supplementary Table 3.