Evaluating the role of Netrin-1 during the early phase of peripheral nerve regeneration using the mouse median nerve model

Abstract

Background: Less is known about the role of Netrin-1 in the peripheral nervous system. In this study, we evaluated the role of Netrin-1 using the mouse median nerve model for assessment of peripheral nerve regeneration. Methods: Using real-time PCR and Western Blot analysis, we examined expression changes of Netrin-1 mRNA and Netrin-1 protein after transection and repair of the mouse median nerve in Wild-type animals. We further evaluated histomorphometrical changes as well as the functional recovery of the grasping force after median nerve transection and repair in WT mice and Netrin-1^+/− heterozygous mice. Results: RT-PCR revealed a 1, 9 fold increase of Netrin-1 mRNA two weeks after nerve transection and repair in the nerve segment distal to the injury site. In Western blot analysis, we could show a high increase of Netrin-1 in the nerve segment distal to the injury site at day 14. Histomorphometrical analysis showed significantly higher cross sectional area and a lower fibre density in heterozygous Netrin-1^+/− mice. Using the functional grasping test, we could show that peripheral nerve regeneration is significantly diminished in heterozygous Netrin-1^+/− mice. Conclusions: Employing the mouse median nerve model in transgenic animals, we demonstrate that Netrin-1 plays an important role during peripheral nerve regeneration.