Fig. 4 The extracellular domain of sortilin is sufficient for BDNF/TrkB signaling. The extracellular domain of sortilin is sufficient for BDNF/TrkB signaling.

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Fig. 4 The extracellular domain of sortilin is sufficient for BDNF/TrkB signaling. The extracellular domain of sortilin is sufficient for BDNF/TrkB signaling. (A) PWT to tactile stimuli of WT mice before and after SNI and intrathecal anti-sortilin antibodies or immunoglobulin G (IgG) injection at day 0. ****P < 0.0001 for ipsilateral anti-sortilin versus ipsilateral IgG; n = 6, two-way RM ANOVA with post hoc Dunnett’s test [F(3,20) = 48.09, P < 0.0001], means ± SEM. (B) PWT to tactile stimuli of WT mice before and after SNI (day 0) and intrathecal anti-sortilin antibodies or IgG injection 6 days after SNI, means ± SEM. (C) Percentage of anti-allodynia by anti-sortilin 1, 2, and 3 hours versus pre-injection baseline (average of days 2 and 6 of the same mouse). *P < 0.03 and **P < 0.001; n = 5, one-way RM ANOVA with post hoc Dunnett’s test [F(3,12) = 9.691, P = 0.0016], means ± SEM. (D) Percentage of anti-allodynia by IgG 1, 2, and 3 hours versus average of days 2 and 6 of the same mouse. n = 5, one-way RM ANOVA with post hoc Dunnett’s test, means ± SEM. (E) PWT to tactile stimuli of Sort1−/− mice before and after SNI (day 0) and intrathecal sol-sortilin or IgG injection (0 hours). *P < 0.02 and ****P < 0.0001, versus the ipsilateral side of intrathecal IgG; n = 4 to 7, two-way RM ANOVA with post hoc Dunnett’s test [F(3,18) = 15.17, P < 0.0001], means ± SEM. (F) PWT to tactile stimuli of WT and Sort1−/− mice before and after intrathecal BDNF ± sol-sortilin injection. ****P < 0.0001 versus Sort1−/− + BDNF injection; n = 6 to 12, two-way RM ANOVA with post hoc Dunnett’s test [F(2,23) = 10.85, P = 0,0005], means ± SEM. Mette Richner et al. Sci Adv 2019;5:eaav9946 Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).