Notch Pathway and the Effect of Apotransferrin on Remyelination

EVANGELINA APARICIO; ANA M. ADAMO

Santa Fe, NM

Congreso; 41st Annual Meeting of the American Society for Neurochemistry; 2010

American Society for Neurochemistry

Previous studies demonstrated that a single intracranial 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).We evaluated the effect of aTf and the possible participation of the Notch pathway in remyelination on lysolecithin(LPC)-induced focal demyelination in the corpus callosum(CC). Adult rats were injected 2%LPC in saline solution (SS) by the stereotaxic technique into the CC.The day of LPC injection was designated as day 0(0 DPL). Seven days later animals were injected a single dose of 350 ng of aTf or SS in the subventricular zone(SVZ) and were sacrificed at different times (2, 6 and 24 h or 3 and 7 days) depending on experiments. A subgroup of animals received one intraventricular injection of the g-secretase inhibitor(DAPT 1mM) before the injection of aTf. To evaluate whether the effects of aTf were due to the protein or to iron, experiments were performed in the presence of desferroxamine(DFX). We observed significant demyelination in the injected area in the CC at 7 DPL and a spontaneous reversion 21 DPL. The injection of aTf induced remyelination 10 DPL. We observed an increase in oligondendrocyte(OL) APC+ population as well as a decrease in OL precursors NG2+ in the CC and SVZ. The injection of DAPT blocked aTf’s effect on remyelination. Experiments with DFX showed no differences in the promyelinating effects of aTF.To explore Notch pathway activation in OL, colocalization of Notch intracellular domain with different OL markers and the expression of down stream genes by RT-PCR were studied. In this model of toxic demyelination, results seem to indicate the involvement of the Notch pathway in the aTF effect on remyelination.