Notch signalling pathway activation during demyelination-remyelination in rats.

FLORENCIA ALMEIRA GUBIANI; MILAGROS PEREIRA LUPPI ; ANA M. ADAMO

Huerta Grande

Congreso; XXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2012

Sociedad Argentina de Investigación en Neurociencia

Notch signalling pathway activation during demyelination-remyelination in rats. Florencia Almeira Gubiani, Milagros Pereira Luppi and Ana M. Adamo. Departamento de Química Biológica, Facultad de Farmcia y Bioquímica, UBA. IQUIFIB-CONICET. A promyelinating effect of aTf in a demyelination model with cuprizone (CPZ) has been demonstrated (Adamo et al 2006). 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 0.6% CPZ diet for 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 evaluated Notch activation throughout NICD level and different Notch ligands (Jagged1 and F3/Contactin) expression by WB and IHC analysis. We also evaluated the expression of 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 mostly in SVZ at -7d and 0d. However,  during spontaneous remyelination (+7d), we observed an increase in NICD level in CC. IHC showed this activation in NG2+ and Nestin+ cells in SVZ of CPZ animals. An increase in Jagged1 was observed during demyelination in SVZ and CC while during remyelination (+7d) we found a significant increase in F3/Contactin level in SVZ.