Apotransferrin enhances differentiation of two oligodendroglial cell lines

Abstract

In the CNS, transferrin (Tf) is produced by oligodendroglial cells (OLGc) and is essential for their survival. A single intracranial injection of apoTf in neonatal rats has been shown to accelerate differentiation of OLG (Marta et al. 2000). Our interest was to study the effect of apoTf at different stages of OLG maturation in two immortalized cell lines, obtained from primary cultures: N19 and N20.1 (Bongarzone et al. 1996). These cell lines grow constantly at 34°C (permissive temperature) and differentiate into mature OLGc at 39°C (nonpermissive temperature). At 34°C, N19 exhibit the characteristics of OLGc precursors (O2A), while N20.1 express markers of mature OLGc (O1, CNPase). In vitro addition of apoTf to the cultures at 39°C during 3 days, showed an increased expression of O1, O4, MBP in both cell lines, a decrease in transferrin receptors and of endogenous Tf. These effects were more evident in the N19 line. ApoTf induces a more mature phenotype of OLGc development in both cells lines. Previous studies have shown that the action of aTf is mediated by its receptor, by the OLGc cytoskeleton and by the activation of protein kinases. OLGc differentation is stimulated by cAMP (Raible and Mc Morris 1990) followed by activation of PKA and elevated levels of CREB (Sato‐Bigbee et al. 1999). In N19 and N20.1 cell lines after seven days in culture in the presence of apoTf, actin expression was mainly located in the OLGc processes, and in the growth cones, while there were no changes in tubulin expression. In the N19, there was a 10‐fold increase in cAMP levels, compared to controls while in the N20.1 there were no changes. These results agree with our previous studies in in vivo experiments and in OLGc primary cultures.