Abstract:
Bidirectional and continuous communication between Schwann cells (SCs) and axons are crucial for peripheral nervous system (PNS) myelin development, maintenance, and repair after injury. Disruption of SCs-axon interaction leads to peripheral neuropathies, therefore, elucidating the molecular mechanisms underlying this interaction is highly important for understanding the etiology of these disorders. FGF1 was suggested to act in peripheral myelination and remyelination by our previous findings. To study remyelination in mouse sciatic nerve, ‘LPC induced demyelination’ model was optimized in another study. In this study, myelin sheath was visualized by immuno-staining and the expression of myelin proteins were analyzed by western blot analysis at different time periods up to three months after LPC injections. The recovery of myelin sheath was shown at three months and accordingly, the level of myelin proteins, MAG and MBP, reached to that of the control group. In the second part of the study, FGF1 involvement in remyelination was further confirmed by FGF1 injections after LPC induced demyelination. The expression of myelin proteins increased significantly 30 minutes after FGF1 injection and reached to the same level with that of the control group in seven days’ time. This observation showed that FGF1 has short term and rapid effects on remyelination, in accordance with the literature. In the last part of the study, the possible interaction partners of FGF1 during peripheral myelination was investigated using dorsal root ganglia co-cultures and precipitating their lysates with Co-IP method. After confirmation of expression of FGF1 protein in DRG co-cultures, its interaction with FGFR1 and MPZ was investigated. FGFR1-FGF1 and MPZ-FGF1 interactions were observed when the precipitates were analyzed by western blot. However, results remained inconclusive due to weak signals that were also observed in control groups. In summary, we have shown that ‘LPC induced demyelination’ model can be used for further analysis as a PNS demyelinating disease model. FGF1 involvement in remyelination was also confirmed. The results from analysis of Co-IP remained elusive that needs of further investigation.
