DIFFERENT NEUREGULIN 1 ISOFORMS ARE EXPRESSED DURING NERVE DEGENERATION, AXON REGENERATION AND REMYELINATION FOLLOWING PERIPHERAL NERVE INJURY

Aims - Peripheral nerve regeneration after traumatic injuries is regulated by the combined action of many factors. One of the most important factors involved in the regulation of Schwann cell (SC) activity is Neuregulin1 (NRG1). The main aim of this project was the expression analysis of the different NRG1 isoforms following nerve injury. Quantitative real-time polymerase chain reaction (qRT-PCR) needs good stable housekeeping genes (HKG) to normalize data. Following nerve injury, the nerve environment is deeply altered by the lesion: SC dedifferentiate and proliferate, macrophages recover myelin debris, axons degenerate and many genes are deeply regulated. A side aim of this project was thus the identification of new HKG which remain stable during all steps of nerve degeneration and regeneration. Methods - Two experimental lesions were performed on adult rats: axonotmesis (crush lesion) and neurotmesis (a complete transection of the nerve, followed by end-to-end repair). Total RNA was extracted from injured nerves at different time points. qRT-PCR for different NRG1 isoforms and corresponding ErbB receptors was carried out. Raw data from two publicly available microarrays were analysed to identify genes which are stable 1, 5 and 7 days following nerve injury. Results & Conclusions -Two stable HKG were identified, validated and used for gene expression analysis. Gene expression analysis shows that in the nerve there is an early up-regulation of soluble glial NRG1 during nerve degeneration, followed by a late up-regulation of transmembrane axonal NRG1 during remyelination. This analysis suggests that each NRG1 isoform plays a specific role following peripheral nerve injury.