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

Figure 2. Dysfunctional BDNF/TrkB signaling correlates with CMT2D pathology.

Figure 2

(A) Representative Western blots of lysates from 5 wild-type muscles, probed with anti-TrkB, displaying a spectrum of vulnerability to NMJ denervation in GarsC201R/+, with the transversus abdominis (TVA) and epitrochleoanconeus (ETA) being least impacted and the flexor digitorum brevis (FDB) displaying the greatest degeneration (33). (B and C) Levels of FL-TrkB (**P = 0.001, 1-way ANOVA) and TrkB.T1 (***P < 0.001, Kruskal-Wallis test) differ between muscles. FL-TrkB (***P < 0.001, Pearson’s product moment correlation), but not TrkB.T1 (P = 0.267 Spearman’s rank correlation), positively correlates with CMT2D denervation. (D) Representative Western blots of lysates from 5 wild-type muscles, probed with anti-GlyRS and anti-CHRNA (quantified in Supplemental Figure 3, C and D). (E and F) Representative collapsed Z-stack confocal images of lumbar spinal cord ventral horns from wild-type and GarsC201R/+ mice stained for ChAT and p-CREB or CREB. Lower panels: inverted fluorescence images. Arrows: motor neuron nuclei. Scale bars = 100 μm. (G and H) GarsC201R/+ lumbar motor neurons display reduced p-CREB activation (G) and are smaller than their wild-type counterparts (H). *P < 0.05, **P < 0.01, ***P < 0.001 unpaired t test. For all graphs, n = 5–6. Mice were P77–P83 (A–D) and 3 months old (E–H). See Supplemental Figures 2–5.