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Fig. 9 | Acta Neuropathologica Communications

Fig. 9

From: Transplantation of induced neural stem cells (iNSCs) into chronically demyelinated corpus callosum ameliorates motor deficits

Fig. 9

Transplantation of iNSCs alters oligodendrocyte populations during recovery. a: Tissues from the cohorts with Miss-step wheel access (Figs. 7 and 8) were further analyzed based on Plp1 transcripts as either low, perinuclear signal (Plp1low) or high and extending into processes (Plp1high). iNSC transplantation increased Plp1low cells during remyelination with wheel running access. b-c: Nuclear Ki67 identified rare proliferating cells. iNSC transplantation increased the proportion of Ki67 cells immunolabeled for the NG2, a marker of OPCs, in the corpus callosum ipsilateral (ipsi) to iNSC/vehicle injections (b). Example of a pair of proliferating OPCs (c, arrows) co-labeled for NG2 and nuclear Ki67 (overlap appears yellow) and quiescent OPCs (c, arrowheads). d-e: Analysis of additional mice without wheel access shows reduced Plp1low cells (d) and increased Plp1high cells (e) during remyelination after chronic CPZ. This difference indicates that Plp1low and Plp1high cells represent distinct lineage stages and/or responses after chronic CPZ. f-h: Cohorts using acute CPZ demyelination to induce extensive remyelination with and without wheel exposure. Without wheels, CPZ decreased Plp1low cells (f) while increasing Plp1high cells (g) as well as newly forming oligodendrocytes identified high expression of Enpp6 (Enpp6high) (h). Miss-step wheel access during remyelination simultaneously reduced Enpp6high cells and increased Plp1low cells (f, h). i: Model integrating expression of Plp1 and Enpp6 transcripts during remyelination after acute and chronic CPZ with iNSC and wheel effects. For oligodendrocyte graphs, bar color reflects condition: no cuprizone (white), cuprizone without wheels (black), cuprizone with wheels (blue), and mice with iNSC (green). Data are mean values ± sem. For chronic CPZ mice from the wheel running cohort, two-way ANOVA was used with Sidak’s multiple comparisons test of CPZ vehicle (n = 10) versus CPZ iNSC (n = 9). Ki67 and NG2 data analyzed using a contingency table with Fisher’s exact test for CPZ vehicle (n = 3) versus CPZ iNSC (n = 3). Chronic CPZ mice without wheel exposure had naïve (n = 5) and CPZ (n = 5) conditions compared by t-tests. The acute CPZ study compared conditions of naïve (n = 6; n = 5 for Enpp6) and CPZ (n = 6) mice with wheel exposure and CPZ (n = 6) mice without wheels using one way ANOVA with Sidak’s multiple comparisons test

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