Regulation of Injury Induced Schwann Cell Proliferation Schwann Cell Proliferation

Abstract: The purpose of this study was to investigate injury induced proliferation of Schwann cells with emphasis of the effects of the insulin-like growth factors (IGF-I and IGF-II) and the sex hormones progesterone and estrogen. Proliferation, measured as [3H] thymidine incorporation, was studied in cultured segments of the rat sciatic nerve or through the use of the thymidine analogue bromo- deoxy-uridine (BrdU) in combination with immunocytochemistry. The latter technique was also used for identification of the proliferating cells in the nerve segments. Exposure of the nerve segments to the truncated or long R3 IGF-1, IGF-II or insulin during 48 h resulted in an increased incorporation of [3H] thymidine. BrdU-labelling revealed that the overwhelming majority of the proliferating cells in the nerve segments were Schwann cells, suggesting that this cell type posses receptors for both the IGF’s and insulin. Estrogen enhanced [3H] thymidine incorporation into male and newborn rats while progesterone stimulated incorporation into segments from females and newborn rats. The results imply that Schwann cells have receptors for estrogen and progesterone and that these receptors like the ones for insulin and the IGF’s may be involved in the control of Schwann cell proliferation. In additional experiments we found that injury induced proliferation of adult Schwann cell proliferation was dependent on Ca2+, calmodulin and protein kinase, while agents, which enhance the formation of cAMP, were inhibitory. These findings are in contrast to the results obtained in cultures of neonatal Schwann cells where agents, which favour c-AMP formation, are mitogenic. Thus, when Schwann cells are maintained in the integrated environment of the nerve, their responses to mitogens are different from those observed in cultures of purified cells. A new model describing how Schwann cells proliferation could be regulated is presented.