Figure 5.
NRG1 promotes reinnervation of targets and functional recovery following peripheral nerve injury. (A) Photomicrographs of transverse sections of glabrous skin from the hind paw of skin 2 months post-injury, arrows identify individual epidermal fibres. (B) Quantification of epidermal innervation, intraepidermal nerve fibre (IENF)/mm, a trend to fewer fibres reinnervating the epidermis 2 months after injury in conNrg1 mutant animals is seen, although this does not reach significance. (C) Photomicrographs of neuromuscular junctions, the gastrocnemius is labelled for: MBP (blue), SV2 and neurofilament marker NF (green) and α-bungarotoxin (red). Neuromuscular junction morphology is normal 8 weeks following sciatic nerve crush in both vehicle control and conNrg1 groups. Note the lack of myelin staining following injury in conNrg1 mutant animals. (D) Quantification of the number of neuromuscular junctions re-innervated at 2 months after sciatic nerve injury. There was a significant reduction in the number of re-innervated neuromuscular junctions in injured conNrg1 animals compared with injured vehicle control animals (*P < 0.05 one-way ANOVA post hoc Tukey), n = 3. (E) Sciatic Functional Index (SFI) was used to assess the functional recovery following sciatic nerve crush. Animals were tested at baseline and post-injury. In conNrg1 mutant animals, functional recovery was significantly slower than vehicle and tamoxifen control animals. conNrg1 versus vehicle control: **P < 0.005 ***P < 0.001 conNrg1 versus tamoxifen control #P < 0.05 ##P < 0.005 two-way repeated measures ANOVA post hoc Tukey. Tamoxifen control, n = 7–8. (F) Representative traces of compound nerve action potentials recorded from the distal tibial nerve after proximal (at crush site) sciatic nerve stimulation of vehicle and conNrg1 mutants. Recording from the uninjured nerve, there is no change in the latency or the amplitude, whereas in the injured nerve, there is an increase in latency and a decrease in the amplitude in mutant animals. (G) Quantification of the conduction velocity. (H) Quantification of the amplitude. *P < 0.05 two tailed Students t-test, n = 4. Tx = tamoxifen; Vh = vehicle.