1. Fig. 7. Treatment with DLK inhibitors reduces p-c-Jun and protects against neuronal and synaptic loss in vitro and in ALS mouse models.
Treatment with DLK inhibitors reduces p-c-Jun and protects against neuronal and synaptic loss in vitro and in ALS mouse models. (A) Quantification of p-c-Jun–positive cells/spinal cord section in SOD1G93A mice after treatment with vehicle (0 mg/kg) or GNE-3511 (37.5 or 75 mg/kg) (n = 5 per group). ANOVA: Significant treatment effect (F2,12 = 11.3, P < ). *P < 0.05 and **P < 0.01,Tukey’s test, versus vehicle (0 mg/kg). (B) Quantification of p-c-Jun–positive cells per section after treatment with vehicle (0 mg/kg) or GNE-8505 (35 mg/kg) (n = 4 per group; ***P < 0.001). (C) Representative images of each dose group shown in (A). Scale bar, 100 μm. (D) Representative images of HB9-GFP–positive motor neurons in the presence (+TF) or absence (−TF) of trophic factors or without trophic factors plus 3.34 μM GNE (E) Quantification of GFP-positive neurite area for trophic factor–deprived motor neurons exposed to increasing concentrations of GNE ANOVA: Significant treatment effect (F3,12 = 9.529, P < 0.01). **P < 0.01, Dunnett’s test, versus vehicle (0 mg/kg) dose group. (F) Quantification of α-bungarotoxin–positive neuromuscular junctions (NMJs) that were either denervated or fully innervated [as measured by proximity to vesicular acetylcholine transporter (VAChT)–positive pixels] in GNE-3511–treated (n = 14) versus vehicle-treated (n = 17) SOD1G93Amice. *P = and **P = versus control littermates. (G) Ratio of denervated to innervated neuromuscular junctions is decreased in GNE-3511–treated SOD1G93Amice. **P < (H) Representative images of neuromuscular junction synapses from vehicle- and GNE-3511–treated SOD1G93A mice. Red, presynaptic side (VAChT); green, postsynaptic side (α-bungarotoxin). White arrows indicate innervated synapses. Scale bars, 50 μm.
Claire E. Le Pichon et al., Sci Transl Med 2017;9:eaag0394
Published by AAAS