CONICET | Buscador de Institutos y Recursos Humanos

In previous studies, we have demonstrated that a single intracranial injection of apotransferrin (aTf) in 3 day old rats produces an increase in the different myelin constituent (Escobar Cabrera, E., 1994,97). This promyelinating effects of aTf were clearly shown in animals suffering demyelination after cuprizone (CPZ) feeding. ApoTf induces a marked increase in the myelin deposition in comparison with the spontaneous remyelination observed in control animals (Adamo et al., 2006). In this study, we examined the possible participation of the Notch signalling pathway in the aTf mediated reversion of demyelination. Twenty one day old Wistar rats were fed a diet containing 0.6% CPZ during two weeks. After withdrawal of CPZ animals were treated with either a single intracranial injection of 350 ng of aTf or saline. At different times after injection (0, 2, 4 and 6 h) rats were used to dissect the subventricular zone (SVZ) and corpus callosum (CC) and to obtain cryostat sections of the brain which were used for immunohistochemistry and Western blot analysis. To explore if the improved remyelination induced by aTf involved Notch pathway activation in the oligodendroglial cells (OLGc), colocalization of Notch intracellular domain (NICD) with different (OLGc) markers by immunohistochemistry and the expression of down stream genes involved in the differentiation of oligodendrocytes precursor cells by RT-PCR were studied. Results show that the level of Notch receptor protein is lower in SVZ from brain of control animals in comparison with CPZ demyelinated rats and that 6 h after the injection of aTf in the SVZ from control rats the expression of Notch receptor increases while it decreases in CPZ treated animals. These results seem to indicate the involvement of Notch pathway in the aTf effect on the remyelination process.