Fig. 1
Neuregulin-1 type 1 (NRG1-I) expression by Schwann cells in various demyelinating neuropathies. a Nrg1-I mRNA expression in sciatic nerves of different rodent models for peripheral neuropathies. Nrg1-I mRNA induction is most pronounced in demyelinating models (PMP22 tg mice, CMT1A model; Mpz−/− mice, model for congenital hypomyelination; EAN rats, experimental autoimmune neuritis) compared to predominant axonal neuropathies (SODG93A tg mice, model for amyotrophic lateral sclerosis; Streptozotocin (STZ)-treated mice, diabetic neuropathy model; Pmp22+/− mice, model for hereditary neuropathy with liability to pressure palsies; Oxaliplatin (OPT)-treated rats, toxic neuropathy model). Sciatic nerves were collected from adult (age 3–4 months) experimental rodents and age-matched controls, respectively (n = 5 per group). Shown is Nrg1-I mRNA expression relative to control level (=1, red line). (Student’s T test). b NRG1-I mRNA expression (standardized to Schwann cell marker S100) is increased in sural nerve biopsies with a demyelinating histopathology (n = 11) compared to controls (n = 4, Student’s T test, left panel). Semithin cross-sections of representative human sural nerve biopsies with high and low NRG1-I expression are shown in right panels (scale bar 10 µm). c Pearson correlation analysis (right panel) of sural nerve NRG1-I mRNA expression and onion bulb frequency reveals a significant positive correlation between NRG1-I expression and the number of onion bulbs (data from b). An electron micrograph exemplarily depicts an onion bulb (scale bar 5 µm). d In CMT1A rats, Nrg1-I mRNA expression in sciatic nerves increases with age and disease progression (n = 4–5 per group, multiple T tests). e Western blot analysis of NRG1 protein (C-terminal antibody) in sciatic nerve lysates of 3-month-old CMT1A rats compared to wild-type animals (n = 3 per group, GAPDH as loading control; for full blots, see Supplementary Figure 5). f Immunohistochemistry on sciatic nerve cross-sections from 3-month-old wild-type (upper panels) and CMT1A mice (lower panels) showing NRG1 expression (green, C terminal SC348 antibody) only in Schwann cells of CMT1A mice. Myelin was stained with MPZ (magenta) and nuclei were with DAPI (blue) (scale bar 2.5 µm). g Quantification of nerve conduction velocity (NCV, left panel) and compound muscle action potential (CMAP) amplitudes (right panel) in P18 mice (wild type n = 10, NRG1cKO n = 14, CMT1A n = 8, CMT1A-NRG1cKO n = 10, one-way analysis of variance (ANOVA) and Tukey’s post test). h Quantification of the number of unmyelinated axons (>1 µm) per area (15,740 µm2) on electron microscopic level of P18 mice (wild type n = 12, NRG1cKO n = 7, CMT1A n = 5, CMT1A-NRG1cKO n = 8, one-way ANOVA and Tukey’s post test). Source data are provided as a source data file. All respective p values are depicted as a range of significance with *p < 0.05; **p < 0.01; and ***p < 0.001
