Notch signalling pathway involvement in the remyelination process

EVANGELINA APARICIO; A.M. ADAMO

Atenas

Congreso; 23 rd. Biennial Meeting of the International Society for Neurochemistry; 2011

International Society for Neurochemistry

Notch signalling pathway involvement in the remyelination process. E. Aparicio, Ana. M. Adamo. Quimica Biológica Patológica. Facultad de Farmacia y Bioquímica. IIHMNO-UBA.IQUIFIB-CONICET,CABA.Argentina Previous studies demonstrate that a single intracraneal injection of apotransferrin (aTf) in 3-day-old rats increases myelin constituents. These promyelinating effects of aTf were shown in cuprizone-demyelinated animals (Adamo et al., 2006) and lysolecithin (LPC)-induced focal demyelination in the corpus callosum (CC). Notch is a family of receptors involved in the proliferation and maturation of oligodendrocytes (OL) during myelination.  We evaluated the effect of aTf and the involvement of the Notch pathway in remyelination in a non-immune toxic model of focal demyelination in the CC. Adult rats were stereotaxically injected 2% LPC into the CC; seven days later they received a single dose of aTf or saline solution (SS). A subset received an intraventricular injection of the g-secretase inhibitor (DAPT) before the aTf injection. Animals were sacrificed at different times after injection depending on experiments. Subventricular zone (SVZ) and CC were dissected for Western blot and Real time PCR. Oligodendrocyte precursor cell (OPC) proliferation was evaluated by incorporation of BrdU. We studied the activation of the Notch pathway by measuring its intracellular domain (NICD) and the expression of downstream genes by Real time PCR. We observed an increase in NICD and Notch ligand Jagged levels in SVZ of demyelinated rats as compared to controls. Concomitantly, we observed an increase in the expression of Hes genes. aTf induced an increase in the Notch ligand F3/contactin after 24h, both in controls and demyelinated animals. According to the activation of the Notch pathway by F3/contactin ligand, Real time results showed an increase in MAG gene expression 24h after aTf injection in LPC animals. Moreover, aTf induced an increase in APC+ OL population, as well as a decrease in OL precursors NG2+ in SVZ and CC. We observed a higher incorporation of BrdU in demyelinated rats compared to controls but aTf induced a decrease in cell proliferation. DAPT injection blocked aTf effects on remyelination. Results hint at the participation of the Notch signalling pathway in remyelination and in the promyelinating effects of aTf.