Notch Pathway involvement in the remyelination and in the promyelinating effect of Apotransferrin.

M. FLOENCIA ALMEIRA GUBIANI ; A. SCHINDER ; A.M. ADAMO

Nueva Orleans

Congreso; Neuroscience 2012; 2012

Neuroscience Society

Notch Pathway involvement in the remyelination and in the promyelinating effect of Apotransferrin. 1Florencia Almeira Gubiani, A. Schinder, and  1A.M. Adamo 1Dept.of Biol. Chem. School of Pharmacy and Biochem.IIMHNO-UBA, IQUIFIB-CONICET, Bs.As., Argentina. In previous studies, we have demonstrated the promyelinating effect of apotransferrin (aTf) in animals suffering demyelination after cuprizone (CPZ) feeding or LPC focal injection. ATf induced a marked increase in myelin deposition as compared to the spontaneous remyelination observed in control animals (C). We have recently demonstrated that as a consequence of demyelination, Jagged1, a ligand of the cannonical pathway of Notch receptor, triggers its activation in neural precursor cells (NPCs) and oligodendrocyte precursor cells (OPCs) present in the subventricular zone (SVZ) of rat brain. Downstream Notch’s Hes genes expression in these cells mediates both OPC proliferation and the commitment of NPCs towards the oligodendroglial progeny. On the other hand, in the corpus callosum (CC), demyelination-mediated Notch activation in OPCs promotes Hes-mediated cell proliferation. In CPZ-demyelinated animals the intraventricular injection of a CAG-GFP retrovirus showed its incorporation into OPCs NG2+ cells present in the SVZ in response to demyelination. The presence of A2B5/GFP+ and MBP/GFP+ cells in the CC 14 days after CAG-GFP retrovirus injection in the SVZ of demyelinated animals suggests that these cells migrate from the SVZ to the CC for remyelination. With these results we studied the possible mechanisms involved in OPC migration during the remyelination process. In this context we observed a higher expression of Shh protein in NG2+ cells in the SVZ of CPZ-treated animals compared to control ones. This increase was observed during demyelination and reverted at the time of CPZ withdrawal. During the spontaneous remyelination an increase in the expression of Shh protein  was observed concomitantly with an increase in NG2+ cell population. These results suggest a possible involvement of Shh pathway in the remyelination process.