Notch Pathway involvement in the remyelination and in the remyelinating effect of

M. FLORENCIA ALMEIRA-GUBIANI; ALEJANDRO SCHINDER; ANA M. ADAMO

Huerta Grande

Congreso; XXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2011

Sociedad Argentina de Investigación en Neurociencia

Notch Pathway involvement in the remyelination and in the promyelinating effect of Apotransferrin. Florencia Almeira Gubiani, Schinder, Alejandro and A.M. Adamo Dept.of Biol. Chem. School of Pharmacy and Biochem.IIMHNO-UBA, IQUIFIB-CONICET, Bs.As., Argentina. We have demonstrated the promyelinating effect of aTf in a demyelination animal model with cuprizone. We examined the Notch signaling pathway in the remyelination process and in the aTf-mediated reversion of demyelination. Twenty-one-day-old Wistar rats were fed with a 0.6% CPZ diet for 2 weeks. After withdrawal of CPZ, animals were treated with either aTf or saline injections. The subventricular zone (SVZ) and corpus callosum (CC) of rats were used for Western blot and RT-PCR. We evaluated the expression of down stream genes Hes1, Hes5 and MAG to explore Notch pathway activation and its relationship with OPC proliferation and differentiation. Results showed an increase in Hes1 expression in the SVZ of CPZ animals when compared to controls and no changes in Hes5 or MAG expression. aTf inyection increased Hes1 and MAG expression after 6h and 24h respectively.  The CC of CPZ-treated animals evidenced a decrease of MAG expression wich was reverted after aTf injection. In order to study the progenitors migration to the demyelinated CC, CAG-GFP retrovirus was injected into SVZ concomitantly with saline, aTf or ã-secretase inhibitor. Analysis at 7 days post injection showed higher incorporation of CAG-GFP virus into SVZ of CPZ- animals as well as colocalization with NG2 and NESTIN.