CONICET | Buscador de Institutos y Recursos Humanos

Demyelination-remyelination in the CNS: possible participation of Notch signaling pathway. Florencia Almeira Gubiani, Milagros Pereira Luppi, Patricia Mathieu and Ana M. Adamo. Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, UBA. IQUIFIB-CONICET. In the CNS the oligodendroglial cell is responsible for normal myelination. Demyelination is a pathological process characterized by myelin loss around axons. Demyelination is followed by remyelination, during this process myelin sheets are restored around demyelinated axons resolving the functional deficit. In this work we examined the Notch signaling pathway involvement in the demyelination-remyelination process in a toxic model of demyelination induced by CPZ ingestion. Twenty-one-day-old Wistar rats were fed with a diet containing 0.6% (w/w) CPZ during 2 weeks. Demyelinated animals were sacrificed 7d before CPZ withdrawal (-7d), the day of CPZ withdrawal (0d), and 7d after (+7d). Control animals were sacrificed at the same time. We characterized Notch signaling in the SVZ and CC throughout NICD level and the non canonical Notch ligand F3/Contactin by WB and IHC analysis. We also evaluated the expression of Notch down stream genes Hes1, Hes5 and MAG in SVZ and CC of control and demyelinated animals by Real Time-PCR. Results showed Notch pathway activation in response to CPZ induced demyelination in SVZ and CC. IHC analysis showed this activation in NG2+ and Olig2+ cells being the percentage of Olig2+ oligodendroglial cells significantly higher than NG2+ oligodendroglial precursor cells (OPC). These results suggest that Notch signaling is involved in the demyelination/remyelination processes and that F3/contactin could mediate OPC differentiation.