Change in the molecular phenotype of Schwann cells upon transplantation into the central nervous system: down-regulation of c-jun
Section snippets
Animals
All experimental procedures were carried out on adult male and female Sprague–Dawley rats (body weight 180–300 g; bred at University College London and the MRC Laboratory of Molecular Biology) deeply anaesthetized with 2% halothane (Fluothane, ICI, U.K.) or with equithesin (4 ml/kg). Sprague–Dawley rat pups aged postnatal day 1 (P1)–P4 were killed by decapitation.
Schwann cells culture
Sciatic nerves were obtained from P1–P4 Sprague–Dawley rat pups, collected in L15 medium (GIBCO, U.K.) treated for 1 h with 0.1%
Fresh peripheral nerve segments crafted into thalamus or cerebellum
We examined by light microscopy 16 grafts, between 6 and 30 dpo; nine grafts had been implanted into the cerebellum, and seven into the thalamus (Table 1).In sections of brain immunostained for Jun, immunopositive neuronal nuclei were present in several brain regions such as the entorhinal cortex, hippocampus and thalamus, in agreement with other studies.[29]In addition, some neurons in the thalamic reticular nucleus and deep cerebellar nuclei were Jun immunoreactive (these data will be
Discussion
The key finding in the present study is that Schwann cells exposed to the CNS environment, whether as components of a freshly transected or predegenerate PN graft, or as a cell suspension of cultured cells, undergo a down-regulation of c-jun expression, as shown both by in situ hybridization and immunohistochemistry. This finding contrasts strongly with observations in the activated Schwann cells of the distal stump of an injured PN in vivo or in isolated Schwann cells in culture; in both of
Conclusions
In conclusion, exposure of Schwann cells to the CNS environment causes a rapid down-regulation of their c-jun levels. In vitro c-jun expression in Schwann cell seems to correlate with their ability to proliferate,[58]as well as their ability to promote neurite outgrowth,[43]thus switching off c-jun in transplanted Schwann cells may be responsible for a reduced ability of Schwann cells to interact with injured CNS axons, and to promote their growth and maturation. The levels of expression of c-
Acknowledgements
We thank Professor A. R. Lieberman for helpful discussion and continued support. We also thank M. Turmaine and S. Miah for help with the electron microscopy and the Wellcome Trust (Grant no. 036926/1.5) for financial support.
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