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. 2023 May 8;8(9):e157191. doi: 10.1172/jci.insight.157191

Figure 6. BDNF specifically rescues axonal transport in CMT2D mice via a Trk-dependent mechanism.

Figure 6

(A) Endosome frame-to-frame speed histograms of 1-month-old GarsC201R/+ mice 4–8 hours posttreatment with vehicle, BDNF, or BDNF plus pan-Trk inhibitor (13 nM PF-06273340). (B) Trk inhibition abrogates the rescue effect of BDNF on GarsC201R/+ endosome transport speed (P = 0.023). (C) Endosomes of GarsC201R/+ mice treated with BDNF and PF-06273340 spend as much time paused as vehicle-treated mice (P < 0.001, Kruskal-Wallis test). (D) Trk inhibition abrogates the positive effect of BDNF on pausing endosomes (P = 0.005). (E) Endosome frame-to-frame speed histograms of 1-month-old GarsC201R/+ mice 4–8 hours posttreatment with vehicle, VEGF165, NT-3, or NT-4. (F–H) VEGF165 impairs GarsC201R/+ endosome transport speed, while NT-3 and NT-4 have no effect (F, P = 0.011). No significant changes in pausing (G, P = 0.086; H, P = 0.323). (I) Endosome frame-to-frame speed histograms of GarsC201R/+ mice treated with vehicle or BDNF for 24 hours, rather than 4–8 hours, before imaging. (J–L) At 24 hours postinjection, BDNF no longer rescues GarsC201R/+ endosome transport speed (J, P = 0.248), percentage time paused (K, P = 0.664), or the percentage of pausing endosomes (L, P = 0.966). Mice were aged P29–P42 (I–L). For all graphs, data were compared using 1-way ANOVAs, unless otherwise stated; *P < 0.05, **P < 0.01, Šídák’s/Dunn’s multiple comparisons test; n = 5–9. The vehicle treatment data are also presented in Figure 1, C and D, and BDNF treatment data in Figure 5, A and B.